@article { ISI:000247546800001, title = {Modified nucleic acid substructures in medicinal chemistry and drug development}, journal = {Current Topics in Medicinal Chemistry}, volume = {7}, number = {7}, year = {2007}, month = {JAN}, pages = {639}, publisher = {BENTHAM SCIENCE PUBL LTD}, type = {Article}, address = {EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES}, issn = {1568-0266}, doi = {10.2174/156802607780487731}, author = {Kumar, Vaijayanti A.} } @article { ISI:000247546800008, title = {Structure-editing of nucleic acids for selective targeting of RNA}, journal = {Current Topics in Medicinal Chemistry}, volume = {7}, number = {7}, year = {2007}, month = {JAN}, pages = {715-726}, publisher = {BENTHAM SCIENCE PUBL LTD}, type = {Article}, address = {EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES}, abstract = {

The synthesis of backbone-modified nucleic acids has been an area of very intense research over the last two decades. The main reason for this research activity is the instability of nucleic acid based drugs in the intracellular conditions. Changes in the sugar-phosphate backbone invariably bring about the changes in the complementation properties of the nucleic acids. The naturally occurring deoxyribose- (DNA) and ribose (RNA) sugar-phosphate backbones are endowed with considerable differences in their binding affinities towards themselves. This occurs because of the different sugar conformations prevalent in DNA and RNA and the subtle structural changes accruing from these in hydrogen bonding, base-stacking interactions and hydration of major/minor grooves. The six-atom phosphodiester linkages and pentose-sugars give immense opportunities for chemical modifications that lead to several backbone-modified nucleic acid structures. This article is focused on such modifications that impart RNA-selective binding properties to the modified nucleic acid mimics and the rationale behind the said selectivity. It is found that the six-atom sugar-phosphate backbone could be replaced by either one-atom extended or one-atom edited repeating units, leading to the folded or extended geometries to maintain the internucleoside distance-complementarity. Other important contributions come from electronegativity of the substituent groups, hydration in the major/minor groove, base stacking etc.

}, issn = {1568-0266}, doi = {10.2174/156802607780487722}, author = {Kumar, Vaijayanti A. and Ganesh, Krishna N.} } @article { ISI:000251868800001, title = {Versatile method for the preparation of conjugates of peptides with DNA/PNA/analog by employing chemo-selective click reaction in water}, journal = {Nucleic Acids Research}, volume = {35}, number = {21}, year = {2007}, month = {DEC}, pages = {e139}, publisher = {OXFORD UNIV PRESS}, type = {Article}, address = {GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND}, abstract = {

The specific 1,3 dipolar Hisgen cycloaddition reaction known as {\textquoteleft}click-reaction{\textquoteright} between azide and alkyne groups is employed for the synthesis of peptideoligonucleotide conjugates. The peptide nucleic acids (PNA)/DNA and peptides may be appended either by azide or alkyne groups. The cycloaddition reaction between the azide and alkyne appended substrates allows the synthesis of the desired conjugates in high purity and yields irrespective of the sequence and functional groups on either of the two substrates. The versatile approach could also be employed to generate the conjugates of peptides with thioacetamido nucleic acid (TANA) analog. The click reaction is catalyzed by Cu (I) in either water or in organic medium. In water, similar to 3-fold excess of the peptide-alkyne/azide drives the reaction to completion in 2 h with no side products.

}, issn = {0305-1048}, doi = {10.1093/nar/gkm935}, author = {Gogoi, Khirud and Mane, Meenakshi V. and Kunte, Sunita S. and Kumar, Vaijayanti A.} } @article { ISI:000252757100011, title = {Chimeric (alpha-amino acid plus nucleoside-beta-amino acid)(n) peptide oligomers show sequence specific DNA/RNA recognition}, journal = {Chemical Communications}, number = {6}, year = {2008}, month = {JAN}, pages = {706-708}, publisher = {ROYAL SOC CHEMISTRY}, type = {Article}, address = {THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND}, abstract = {

An alpha/beta-peptide backbone oligonucleotide comprising natural alpha-amino acids alternating with a beta-amino acid component derived from thymidine sequence specifically recognizes and binds to deoxy- and ribo-oligoadenylates in triplex mode.

}, issn = {1359-7345}, doi = {10.1039/b716835g}, author = {Gogoi, Khirud and Kumar, Vaijayanti A.} } @article { ISI:000253152700039, title = {Ferrocene-linked thymine/uracil conjugates: base pairing directed self-assembly and supramolecular packing}, journal = {Journal of Organic Chemistry}, volume = {73}, number = {4}, year = {2008}, month = {FEB}, pages = {1508-1515}, publisher = {AMER CHEMICAL SOC}, type = {Article}, address = {1155 16TH ST, NW, WASHINGTON, DC 20036 USA}, abstract = {

Ferrocene-linked bis(nucleobase) (la-c) and chimeric nucleobase (1d) conjugates have been synthesized from mono- and bis(hydroxybutyl)ferrocene 6 via Mitsunobu reaction as the key step. X-ray crystallographic studies of ferrocene bis(nucleobase) conjugates reveal two-dimensional supramolecular organizations of backbones through self-assembled Watson-Crick and reverse Watson-Crick type pairs. Ferrocene-bis(thymine) conjugate self-assembles by reverse Watson-Crick pairing, while the corresponding bis(uracil) conjugate self-assembles by alternating WC and reverse WC type pairing. Such continuous assemblies are not seen in monosubstituted ferrocene nucleobase conjugates which form only planar sheets. The results are interesting from the point of understanding and engineering supramolecular assemblies through rational design of base pairing patterns.

}, issn = {0022-3263}, doi = {10.1021/jo7023416}, author = {Patwa, Amit N. and Gupta, Susmita and Gonnade, Rajesh G. and Kumar, Vaijayanti A. and Bhadbhade, Mohan M. and Ganesh, Krishna N.} } @article { ISI:000207861902126, title = {CARB 36-Novel and structurally biased backbone modifications of nucleic acids}, journal = {Abstracts of Papers of the American Chemical Society}, volume = {238}, year = {2009}, month = {AUG}, pages = {Meeting Abstract : 36-CARB}, publisher = {AMER CHEMICAL SOC}, type = {Meeting Abstract}, address = {1155 16TH ST, NW, WASHINGTON, DC 20036 USA}, issn = {0065-7727}, author = {Kumar, Vaijayanti A.} } @article { ISI:000271506600038, title = {Effect of chirality of L/D-proline and prochiral glycine as the linker amino acid in five-atom linked thymidinyl-(alpha-aminoacid)-thymidine dimers}, journal = {Chemical Communications}, number = {43}, year = {2009}, month = {SEP}, pages = {6646-6648}, publisher = {ROYAL SOC CHEMISTRY}, address = {THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND}, abstract = {

The chirality of the amide linker in dimer blocks was found to have a profound effect on the orientation of base stacking interactions as studied by CD and NMR spectroscopy.

}, issn = {1359-7345}, doi = {10.1039/b913546d}, author = {Seema Bagmare and D{\textquoteright}Costa, Moneesha and Kumar, Vaijayanti A.} } @article { ISI:000263732700047, title = {Effects for the incorporation of five-atom thioacetamido nucleic acid (TANA) backbone on hybridization thermodynamics and kinetics of DNA duplexes}, journal = {Journal of Physical Chemistry B}, volume = {113}, number = {9}, year = {2009}, month = {MAR}, pages = {2944-2951}, publisher = {AMER CHEMICAL SOC}, address = {1155 16TH ST, NW, WASHINGTON, DC 20036 USA}, abstract = {

Thermodynamic studies of nucleic acids serve not only to widen our understanding on the nature and strength of forces that stabilize nucleic acids in a myriad of structural states they assume but also to facilitate the development of databases that could be used to predict the stability and selectivity of probe/primer-sets required in a broad range of nucleic acid-based diagnostic and therapeutic protocols. In the current study, we investigated the effect of a novel, backbone-modified {\textquoteleft}{\textquoteleft}thioacetamido linkage{\textquoteright}{\textquoteright} (TANA) on thermodynamics of hybridization, binding kinetics, and conformation of a DNA duplex. The modification comprises of an extended five-atom amide (N3{\textquoteright}-CO-CH(2)-S-CH(2)) linker, as opposed to four-atom phosphodiester linker backbone present in DNA. One to three TANA-substitutions have been introduced in the linker backbone of two thymidine residues of one of the strand of the DNA duplex. Using spectroscopic and calorimetric techniques, we observed that TANA destabilizes the DNA helix by lowering the favorable enthalpy parameter of duplex formation. TANA center dot DNA duplexes were found to adopt a conformation toward an A-type duplex as shown by circular dichroism spectroscopy studies. Analysis of differential scanning calorimetry data indicated a nonzero heat capacity change, Delta C(p), accompanying the duplex formation. The average Delta C(p) change per duplex was found to be 832.5 cal mol(-1) K(-1), giving an average base-pair change of 59.5 cal (mol of base pairs)(-1) K(-1). Hybridization kinetic measurements using surface plasmon resonance indicated a decrease in binding affinity parameter (K(A)) that originates from higher dissociation rate constants (k(d)). Furthermore, optical melting studies showed that increasing the number of modifications results in a modest change in the number of counterions taken up during duplex formation.

}, issn = {1520-6106}, doi = {10.1021/jp808747g}, author = {Kaur, Harleen and Arora, Amit and Gogoi, K. and Solanke, P. and Gunjal, Anita D. and Kumar, Vaijayanti A. and Maiti, Souvik} } @article { ISI:000280527500021, title = {Amino/guanidino-functionalized N-(pyrrolidin-2-ethyl)glycine-based pet-PNA: design, synthesis and binding with DNA/RNA}, journal = {Organic \& Biomolecular Chemistry}, volume = {8}, number = {16}, year = {2010}, month = {JUN}, pages = {3742-3750}, publisher = {ROYAL SOC CHEMISTRY}, address = {THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND}, abstract = {

The N-(pyrrolidin-2-ethyl) glycine-based PNA (pet-PNA) backbone, with 4-amino or 4-guanidino-functionalized pyrrolidine ring, confers constrained conformational flexibility on aegPNA. The oligomers bind to the target DNA and RNA sequences with increased sequence specificity and antiparallel versus parallel orientation selectivity. The easy post-synthetic guanidination gives very good access to the positively charged PNA oligomers.

}, issn = {1477-0520}, doi = {10.1039/c004005c}, author = {Gokhale, Sachin S. and Kumar, Vaijayanti A.} } @article { ISI:000280527500020, title = {Design, synthesis and DNA/RNA binding studies of nucleic acids comprising stereoregular and acyclic polycarbamate backbone: polycarbamate nucleic acids (PCNA)}, journal = {Organic \& Biomolecular Chemistry}, volume = {8}, number = {16}, year = {2010}, month = {Jun}, pages = {3734-3741}, publisher = {ROYAL SOC CHEMISTRY}, address = {THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND}, abstract = {

The designed, chiral, acyclic polycarbamate nucleic acids (PCNA) exhibited sequence and orientation specific binding to nucleic acids. Complexes of PCNA with DNA were as stable as PNA:DNA complexes and those with RNA were as stable as natural DNA:RNA complexes.

}, issn = {1477-0520}, doi = {10.1039/c003405n}, author = {Madhuri, Vangala and Kumar, Vaijayanti A.} } @article { ISI:000285081100050, title = {Ferrocene-Bis(thymine/uracil) conjugates: base pairing directed, spacer dependent self-assembly and supramolecular packing}, journal = {Journal of Organic Chemistry}, volume = {75}, number = {24}, year = {2010}, month = {DEC}, pages = {8705-8708}, publisher = {AMER CHEMICAL SOC}, address = {1155 16TH ST, NW, WASHINGTON, DC 20036 USA}, abstract = {

X-ray crystallographic studies of methylene linked Ferrocene-bis(thymine/uracil) conjugates Fc(T:T)m and Fc(U:U)(M) reveal base dependent 2-D supramolecular assemblies generated via wobble self-pairing for bis-thymine and reverse wobble self-pairing for bis-uracil conjugates, differing in architecture from the corresponding butylene spacer linked conjugates

}, issn = {0022-3263}, doi = {10.1021/jo101813z}, author = {Patwa, Amit N. and Gonnade, Rajesh G. and Kumar, Vaijayanti A. and Bhadbhade, Mohan M. and Ganesh, Krishna N.} } @article { ISI:000283531100049, title = {Probing binding preferences of DNA and RNA: backbone chirality of thioacetamido-linked nucleic acids and iso-thioacetamido-linked nucleic acids to differentiate DNA versus RNA selective binding}, journal = {Journal of Organic Chemistry}, volume = {75}, number = {21}, year = {2010}, month = {NOV}, pages = {7431-7434}, publisher = {AMER CHEMICAL SOC}, address = {1155 16TH ST, NW, WASHINGTON, DC 20036 USA}, abstract = {

Subtle differences in RNA and DNA duplex geometry could be sensed by the changed stereochemistry at 3 {\textquoteleft}-amino function in the 5-atom thioacetamido linker of thioacetamido-linked nucleic acids and iso-thioacetamido-linked nucleic acids modified oligomers. In contrast to the preferred N-type sugar conformations for either 3 {\textquoteleft}- ribo- or xylo amino nucleosides, predominant S-type sugar conformations were found in the dimers. Although the CD spectral differences for the dimer blocks were found to be identical for those found in phosphodiester linked ribo/xylo dimers, the 5-atom thioactamido linker could reverse the RNA binding selectivity to DNA binding selectivity by the change in configuration at the 3 {\textquoteleft}-amino-substituted sugar.

}, issn = {0022-3263}, doi = {10.1021/jo1014036}, author = {Gokhale, Sachin S. and Gogoi, Khirud and Kumar, Vaijayanti A.} } @article { ISI:000288386600095, title = {Probing the furanose conformation in the 2 {\textquoteleft}-5 {\textquoteleft} strand of isoDNA:RNA duplexes by freezing the nucleoside conformations}, journal = {Chemical Communications}, volume = {47}, number = {13}, year = {2011}, month = {FEB}, pages = {4007-4009}, publisher = {ROYAL SOC CHEMISTRY}, address = {THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND}, abstract = {

Sugar conformations in the isoDNA strand of isoDNA : RNA duplexes are preferred S-type locked/frozen in contrast to N-type locked conformations preferred in DNA: RNA duplexes.

}, issn = {1359-7345}, doi = {10.1039/c0cc05402j}, author = {Erande, Namrata D. and Gunjal, Anita D. and Fernandes, Moneesha and Kumar, Vaijayanti A.} } @article { ISI:000293119900005, title = {Robust synthesis of enantiopure cyclohexenyl analogues of 2/3-deoxyribose sugars as carbocyclic nucleoside precursors}, journal = {Tetrahedron}, volume = {67}, number = {32}, year = {2011}, month = {AUG}, pages = {5744-5749}, publisher = {PERGAMON-ELSEVIER SCIENCE LTD}, address = {THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND}, abstract = {

An expedient synthesis of 2-deoxy (10) and 3-deoxy (11) cyclohexenyl analogues of 2-deoxy and 3-deoxy-D-ribose sugar from commercially available starting materials is reported. Highly efficient enzymatic resolution of the key compound 10 is described using lipase under hydrolytic conditions. The robust methodology applied here will be useful to synthesize cyclohexenyl nucleosides, which possess potent antiviral activity and are capable of gene silencing via RNAi or antisense applications. (C) 2011 Elsevier Ltd. All rights reserved.

}, keywords = {Carbocyclic mimics of 2-deoxy-D-ribose and 3-deoxy-D-ribose Enzymatic resolution, CeNA, DA reaction}, issn = {0040-4020}, doi = {10.1016/j.tet.2011.06.003}, author = {Varada, Manojkumar and Kotikam, Venubabu and Kumar, Vaijayanti A.} } @article { ISI:000302276700009, title = {Design and synthesis of dephosphono dna analogues containing 1,2,3-triazole linker and their UV-melting studies with DNA/RNA}, journal = {Nucleosides Nucleotides \& Nucleic Acids}, volume = {31}, number = {1-3}, year = {2012}, month = {JAN}, pages = {97-111}, publisher = {TAYLOR \& FRANCIS INC}, address = {530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA}, abstract = {

This article describes the synthesis of 3{\textquoteright}/5{\textquoteright} linked 1,2,3-triazolyl dithymidine derivatives, their incorporation into oligonucleotides, and evaluation of their thermal stabilities toward complementary DNA/RNA.

}, keywords = {isostere, Oligonucleotide analogues, Triazole, UV melting}, issn = {1525-7770}, doi = {10.1080/15257770.2011.644100}, author = {Madhuri, Vangala and Kumar, Vaijayanti A.} } @article { ISI:000303362900001, title = {Highly efficient (R-X-R)-type carbamates as molecular transporters for cellular delivery}, journal = {Journal of the American Chemical Society}, volume = {134}, number = {17}, year = {2012}, month = {MAY}, pages = {7196-7199}, publisher = {AMER CHEMICAL SOC}, address = {1155 16TH ST, NW, WASHINGTON, DC 20036 USA}, abstract = {

The (R-X-R) motif-containing arginine-rich peptides are among the most effective cell-penetrating peptides. The replacement of amide linkages in the (R-X-R) motif by carbamate linkages as in (r-ahx-r)(4) or (r-ahx-r-r-apr-r)(2) increases the efficacy of such oligomers several-fold. Internalization of these oligomers in mammalian cell lines occurs by an energy-independent process. These oligomers show efficient delivery of biologically active plasmid DNA into CHO-K1 cells.

}, issn = {0002-7863}, doi = {10.1021/ja210026m}, author = {Patil, Kiran M. and Naik, Rangeetha J. and Rajpal and Fernandes, Moneesha and Ganguli, Munia and Kumar, Vaijayanti A.} } @article { ISI:000320838200014, title = {C-3 {\textquoteleft}-endo-puckered pyrrolidine containing PNA has favorable geometry for RNA binding: novel ethano locked PNA (ethano-PNA)}, journal = {Bioorganic \& Medicinal Chemistry}, volume = {21}, number = {14}, year = {2013}, month = {JUL}, pages = {4092-4101}, publisher = {PERGAMON-ELSEVIER SCIENCE LTD}, address = {THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND}, abstract = {

A novel peptide nucleic acid (PNA) analogue is designed with a constraint in the aminoethyl segment of the aegPNA backbone so that the dihedral angle beta is restricted within 60-80 degrees, compatible to form PNA:RNA duplexes. The designed monomer is further functionalized with positively charged amino-/guanidino-groups. The appropriately protected monomers were synthesized and incorporated into aegPNA oligomers at predetermined positions and their binding abilities with cDNA and RNA were investigated. A single incorporation of the modified PNA monomer into a 12-mer PNA sequence resulted in stronger binding with complementary RNA over cDNA. No significant changes in the CD signatures of the derived duplexes of modified PNA with complementary RNA were observed. (C) 2013 Elsevier Ltd. All rights reserved.

}, keywords = {Antisense therapeutics, Conformationally constrained PNA, Diagnostics, Peptide nucleic acid (PNA)}, issn = {0968-0896}, doi = {10.1016/j.bmc.2013.05.015}, author = {Banerjee, Anjan and Kumar, Vaijayanti A.} } @article { ISI:000319335700004, title = {Detection and knockdown of MicroRNA-34a using thioacetamido nucleic acid}, journal = {Nucleic Acid Therapeutics}, volume = {23}, number = {3}, year = {2013}, month = {JUN}, pages = {195-202}, publisher = {MARY ANN LIEBERT INC}, address = {140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA}, abstract = {

Thioacetamido nucleic acids (TANA) contain a backbone modification of dinucleotides consisting of a 5-atom amide linker N3{\textquoteright}-COCH2-S-CH2 at thymidine or thymidine-cytidine dimer blocks. Here, the chemical synthesis of the TANA linked 5-methyl-cytidine-cytidine ((Me)cc) dimer block and its incorporation into the DNA sequence, complementary to human microRNA 34 (miR-34) is described. Further, for the first time, we demonstrate the biological applications of TANA modified oligonucleotides in detection and intracellular knockdown of a cancer related microRNA in comparison with DNA containing locked nucleic acid (LNA) and 2{\textquoteright}-O-methyl modifications. The human microRNA miR-34 is a pro-apoptotic microRNA under the transcriptional control of protein 53 (p53). It gets expressed in response to DNA damage and regulates several cell cycle and apoptosis related targets. Here, we show that the TANA modified antisense oligonucleotide binds specifically to miR-34a, allowing its detection using primer extension. We also show that, using the TANA modified antisense oligonucleotide against miR-34a, intracellular levels of miR-34 can be reduced, and consequently, the expression of its target oncogene V-myc myelocytomatosis viral related oncogene, neuroblastoma derived (MYCN) is enhanced. Further, we assessed the toxicity and serum stability of the oligonucleotide to conclude that it is suitable for detection and modulation of the vital biomarker and tumor suppressor microRNA.

}, issn = {2159-3337}, doi = {10.1089/nat.2012.0411}, author = {Soni, Kartik and Gupta, Shivani and Gokhale, Sachin S. and Dey, Rakesh and Gunjal, Anita D. and Kumar, Vaijayanti A. and Pillai, Beena} } @article { ISI:000321231700008, title = {Synthesis and properties of 2 {\textquoteleft}-O-[R- and S-(2-amino-3-methoxy)propyl] (R-AMP and S-AMP) nucleic acids}, journal = {Tetrahedron}, volume = {69}, number = {31}, year = {2013}, month = {AUG}, pages = {6404-6408}, publisher = {PERGAMON-ELSEVIER SCIENCE LTD}, address = {THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND}, abstract = {

Substitution at 2{\textquoteright}-position by either amino- or methoxy-pendant groups of the antisense oligonucleotides (AONs) is known to enhance their therapeutic value. A simple modification is described here in which we introduce both these groups in the form of enantiospecific tethers at 2{\textquoteright}-position. Practical synthesis of modified nucleosides using natural L-serine, en route to R-AMP- and S-AMP-AONs is presented. Such tethered ONs formed stable DNA:RNA duplexes and the stability was found to be marginally better than the methoxyethyl/methoxypropyl-substituted MOE/MOP-AONs. The stereochemistry of the tether effectively differentiated the hydrolytic cleavage of AONs and the R-AMP-AON was three times more stable than the S-AMP-AONs after 4 h. In comparison, the MOE- or MOP-AONs were almost completely digested by SVPD after 1 h. (C) 2013 Elsevier Ltd. All rights reserved.

}, keywords = {Antisense therapeutics, MOE-AONs, Positively charged ON analogues}, issn = {0040-4020}, doi = {10.1016/j.tet.2013.05.104}, author = {Kotikam, Venubabu and Kumar, Vaijayanti A.} } @article { ISI:000312946200007, title = {Synthesis and structural studies of S-type/N-type-locked/frozen nucleoside analogues and their incorporation in RNA-selective, nuclease resistant 2 {\textquoteleft}-5 {\textquoteleft} linked oligonucleotides}, journal = {Organic \& Biomolecular Chemistry}, volume = {11}, number = {5}, year = {2013}, month = {NOV}, pages = {746-757}, publisher = {ROYAL SOC CHEMISTRY}, address = {THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND}, abstract = {

2{\textquoteright}-endo locked or frozen (S-type)/3{\textquoteright}-endo locked or frozen (N-type) nucleoside analogues were synthesized. Conformational analysis based on (3)J(HH) and NOE measurements is presented which is further confirmed by X-ray crystal structural studies. 2{\textquoteright}-5{\textquoteright} isoDNA oligonucleotides (ON) were synthesized using these modified nucleoside analogues and UV-T-m studies of the resultant 2{\textquoteright}-5{\textquoteright} isoDNA : RNA duplexes reflect the site-and sequence-dependent effects and confirm that the S-type sugar conformations were preferred over the N-type sugar geometry in such duplexes.

}, issn = {1477-0520}, doi = {10.1039/c2ob26762d}, author = {Erande, Namrata D. and Gunjal, Anita D. and Fernandes, Moneesha and Gonnade, Rajesh G. and Kumar, Vaijayanti A.} } @article { ISI:000315060600030, title = {Synthesis of all four nucleoside-based beta-amino acids as protected precursors for the synthesis of polyamide-DNA with alternating alpha-amino acid and nucleoside-beta-amino acids}, journal = {Tetrahedron}, volume = {69}, number = {3}, year = {2013}, month = {JAN}, pages = {1210-1216}, publisher = {PERGAMON-ELSEVIER SCIENCE LTD}, address = {THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND}, abstract = {

A simple approach is described for the synthesis of all four orthogonally protected nucleoside-beta-amino acids from commercially available starting materials. Synthesis of a model tetrameric DNA sequence in 5{\textquoteright}-3{\textquoteright}direction employing trityl strategy and glycine as alpha-amino acid alternating with nucleoside-beta amino acids is described. (C) 2012 Elsevier Ltd. All rights reserved.

}, keywords = {Antisense therapeutics, Neutral DNA analogues, Nucleoside-beta amino acids}, issn = {0040-4020}, doi = {10.1016/j.tet.2012.11.028}, author = {Seema Bagmare and Varada, Manojkumar and Banerjee, Anjan and Kumar, Vaijayanti A.} } @article { ISI:000328650000032, title = {Functional isoDNA aptamers: modified thrombin binding aptamers with a 2{\textquoteright}-5{\textquoteright}-linked sugarphosphate backbone (isoTBA)}, journal = {Chemical Communications}, volume = {50}, number = {5}, year = {2014}, month = {NOV}, pages = {605-607}, publisher = {ROYAL SOC CHEMISTRY}, address = {THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND}, abstract = {

The regioisomeric 3{\textquoteright}-deoxy-2{\textquoteright}-5{\textquoteright}-linked thrombin binding DNA aptamers (isoTBAs) were chemically synthesized and their ability to form unimolecular anti-parallel G-quadruplexes in the presence of K+ ions was evaluated. These modified sequences retain the function of the native thrombin binding aptamer (TBA), exhibit better stability against exonuclease and are capable of slowing down the process of blood clotting.

}, issn = {1359-7345}, doi = {10.1039/c3cc47569g}, author = {Gunjal, Anita D. and Fernandes, Moneesha and Erande, Namrata D. and Rajamohanan, P. R. and Kumar, Vaijayanti A.} } @article { ISI:000341339300024, title = {Second generation, arginine-rich (R-X {\textquoteleft}-R)(4)-type cell-penetrating alpha-omega-alpha-peptides with constrained, chiral omega-amino acids (X {\textquoteleft}) for enhanced cargo delivery into cells}, journal = {Bioorganic \& Medicinal Chemistry Letters}, volume = {24}, number = {17}, year = {2014}, month = {SEP}, pages = {4198-4202}, publisher = {PERGAMON-ELSEVIER SCIENCE LTD}, address = {THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND}, abstract = {

The syntheses of novel N-aminoalkyl proline-derived spacers (X{\textquoteright}) in polycationic (R-X{\textquoteright}-R)-motif cell-penetrating alpha-omega-alpha-peptides are described as improved molecular transporters and their structural features studied by CD. FACS analysis shows enhanced cellular uptake and confocal microscopy indicates predominantly cytoplasmic localization. The oligomers are efficient at transporting pDNA into cells. The chirality together with the hydrophobicity and flexibility derived from the spacer chain are found to have marked influence on the cell-penetrating and cargo delivery properties of the cell-penetrating peptides (CPPs). The peptides containing N-(3-aminopropyl)-D-proline spacers are found to be the best at cell penetration and cargo delivery in the present study. (C) 2014 Elsevier Ltd. All rights reserved.

}, keywords = {(R-X-R)-motif, alpha-omega-alpha-Peptide, Cell-penetrating peptide, Constrained chiral amino acid, Peptidomimetics}, issn = {0960-894X}, doi = {10.1016/j.bmcl.2014.07.040}, author = {Patil, Kiran M. and Naik, Rangeetha J. and Vij, Manika and Yadav, Amit K. and Kumar, Vaijayanti A. and Ganguli, Munia and Fernandes, Moneesha} } @article { ISI:000344471800052, title = {Simple molecular engineering of glycol nucleic acid: progression from self-pairing to cross-pairing with cDNA and RNA}, journal = {Bioorganic \& Medicinal Chemistry}, volume = {22}, number = {21}, year = {2014}, month = {NOV}, pages = {6227-6232}, publisher = {PERGAMON-ELSEVIER SCIENCE LTD}, address = {THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND}, abstract = {

The acyclic chiral nucleic acid analogue, Glycol Nucleic Acid (GNA), displayed exceptional structural simplicity and atom economy while forming self-paired duplexes, using canonical Watson-Crick base pairing. We disclose here that the replacement of phosphodiester linker in GNA with somewhat rigid and shorter carbamate linker in Glycol Carbamate Nucleic Acid (GCNA) backbone allows unprecedented stability to the antiparallel self-paired duplexes. The R-GCNA oligomers were further found to form cross-paired antiparallel duplexes with cDNA and RNA following Watson-Crick base pairing. The stability of cross-paired GCNA: DNA and GCNA: RNA duplexes was higher than the corresponding DNA: DNA and DNA: RNA duplexes. The chiral (R) and (S) precursors were easily accessible from naturally occurring L-serine. (C) 2014 Elsevier Ltd. All rights reserved.

}, keywords = {Acyclic chiral nucleic acid, Cross-pairing, GCNA, GNA, Self-pairing}, issn = {0968-0896}, doi = {10.1016/j.bmc.2014.08.022}, author = {Bose, Tanaya and Kumar, Vaijayanti A.} } @article { ISI:000353218700026, title = {Beta, gamma-Bis-substituted PNA with configurational and conformational switch: preferred binding to cDNA/RNA and cell-uptake studies}, journal = {Chemical Communications}, volume = {51}, number = {36}, year = {2015}, month = {MAR}, pages = {7693-7696}, publisher = {ROYAL SOC CHEMISTRY}, type = {Article}, address = {THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND}, abstract = {

(S,S)- and (R,R)-beta,gamma-Bis-substituted PNAs were synthesized from the C-2 symmetric vicinal diamine system embedded in 1,4 dihydroxybutane and 1,4-dimethoxybutane scaffolds. (R,R)-beta,gamma-Bis-methoxymethyl-PNA derived from D-tartaric acid was found to be in the right configuration and conformation to be an excellent mimic of PNA, endowed with superior ability to enter into cells.

}, issn = {1359-7345}, doi = {10.1039/c5cc00891c}, author = {Bose, Tanaya and Banerjee, Anjan and Nahar, Smita and Maiti, Souvik and Kumar, Vaijayanti A.} } @article { ISI:000365220100089, title = {Ene-nucleic acids: a different paradigm to DNA chemistry}, journal = {RSC Advances}, volume = {5}, number = {118}, year = {2015}, month = {NOV}, pages = {97824-97830}, publisher = {ROYAL SOC CHEMISTRY}, address = {THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND}, abstract = {

Acyclic prochiral nucleic acids such as FNA, UNA, GNA and cyclic chiral TNA are all considered as precursors of DNA and RNA in the chemical etiology of nucleic acids. The chemical reasoning would suggest that unsaturated precursors with constrained flexibility and selectivity based on cis/trans isomers could be the missing link between the prochiral-acyclic and chiral-cyclic structures mentioned above. We find that ene-nucleic acids derived from an isoprenoid skeleton possess requisite flexibility and rigidity while forming stable duplex structures with complementary DNA and RNA.

}, issn = {2046-2069}, doi = {10.1039/c5ra15673d}, author = {Varada, Manojkumar and Erande, Namrata D. and Kumar, Vaijayanti A.} } @article { ISI:000359962900040, title = {Glycine-linked nucleoside-beta-amino acids: polyamide analogues of nucleic acids}, journal = {Bioconjugate Chemistry}, volume = {26}, number = {8}, year = {2015}, month = {AUG}, pages = {1737-1742}, publisher = {AMER CHEMICAL SOC}, address = {1155 16TH ST, NW, WASHINGTON, DC 20036 USA}, abstract = {

3{\textquoteright}-5{\textquoteright}-Deoxyribose-sugar-phoshate backbone in DNA is completely replaced by 2{\textquoteright}-deoxyribonucleoside-based beta-amino acids interlinked by glycine to create uncharged polyamide DNA with 3{\textquoteright}-5{\textquoteright}-directionality. These oligomers as conjugates of alpha-amino acids and nucleoside-beta-amino acids bind strongly and sequence-specifically only to the antiparallel complementary RNA and DNA.

}, issn = {1043-1802}, doi = {10.1021/acs.bioconjchem.5b00296}, author = {Banerjee, Anjan and Seema Bagmare and Varada, Manojkumar and Kumar, Vaijayanti A.} } @article { ISI:000352668900015, title = {Investigation of the effect of amino acid chirality in the internucleoside linker on DNA:DNA and DNA : RNA duplex stability}, journal = {Tetrahedron}, volume = {71}, number = {16}, year = {2015}, month = {APR}, pages = {2442-2449}, publisher = {PERGAMON-ELSEVIER SCIENCE LTD}, type = {Article}, address = {THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND}, abstract = {

Enzymatically and chemically stable amide-linked di/oligonucleosides are highly desired synthetic targets in which the phosphodiester linkages in native DNA are replaced by amide linkers of appropriate length and stereochemistry. The five-atom amide-linked dimers, synthesized from 3{\textquoteright}-amino-3{\textquoteright}-deoxy thymidine, (alpha-(L/D) proline/prochiral glycine and thymidine/uridine-4{\textquoteright}carboxylic acid derivatives, were incorporated into the DNA backbone to achieve partial replacement of selected phosphodiester linkages. The results stressed the importance of the chirality of linker amino acid. D-Proline was found to be the most compatible as an internucleoside linker in the DNA backbone to stabilize the complexes with DNA or RNA as compared to L-proline and glycine. (C) 2015 Elsevier Ltd. All rights reserved.

}, keywords = {alpha-Amino acid, Chiral amide linkage, DNA, Five-atom amide linkage, L/D-Proline}, issn = {0040-4020}, doi = {10.1016/j.tet.2015.02.042}, author = {Seema Bagmare and Gunjal, Anita D. and Kumar, Vaijayanti A.} } @article { ISI:000359951700161, title = {RXR-carbamate - a novel molecular transporter for skin}, journal = {Molecular Therapy}, volume = {23}, number = {1}, year = {2015}, note = {18th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT), New Orleans, LA, MAY 13-16, 2015}, month = {MAY}, pages = {S64-S64}, publisher = {Amer Soc Gene \& Cell Therapy}, address = {75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA}, issn = {1525-0016}, author = {Natarajan, Poornemaa and Patil, Kiran M. and Vij, Manika and Yadav, Amit K. and Kumar, Vaijayanti A. and Ganguli, Munia and Fernandes, Moneesha} } @article {42435, title = {Unimolecular antiparallel G-quadruplex folding topology of 2{\textquoteright}-5{\textquoteright}-isoTBA sequences remains unaltered by loop composition}, journal = {Organic \& Biomolecular Chemistry}, volume = {13}, year = {2015}, month = {OCT}, pages = {11696-11703}, type = {Journal Article}, abstract = {

A 2{\textquoteright}-5{\textquoteright}-linked isoTBA 15 mer sequence with (232) loop composition formed stable antiparallel quadruplex structures similar to the SELEX derived 15 mer TBA sequence with (232) loop composition. A parallel versus antiparallel topology of 3{\textquoteright}-5{\textquoteright}-G-quadruplexes is largely dictated by the loop length, and it is known that the truncated loops favour parallel quadruplexes. In contrast to TBA, systematic reduction of the loop length in isoTBA from (232) to (222), (131) or even (111) did not alter the antiparallel topology of the resulting 14 mer, 13 mer and 11 mer G-rich modified isoTBA-like sequences.

}, doi = {10.1039/c5ob01923k}, author = {Aher, Manisha N.}, editor = {Erande, Namrata D.} } @article {45819, title = {4 {\textquoteleft}-Epi-DNA: A DNA Mimic Containing 4 {\textquoteleft}-hydroxymethyl-alpha-l-Xylo-thymidine with compact backbone like RNA}, journal = {Nucleosides Nucleotides \& Nucleic Acids}, volume = {35}, year = {2016}, month = {APR}, pages = {445-458}, type = {Article}, abstract = {

Synthesis of C4-epi-DNA containing 3 5 linkages is reported for the first time. Crystal structure study of the monomer indicated that though the dihedral angle O3-C3-C4-C5 in this case would be like in RNA, the sugar conformation would remain like that in DNA. The study of the effect of this backbone configuration in DNA with respect to its binding to cDNA and RNA is reported in this note.

}, keywords = {4 {\textquoteleft}-hydroxymethyl nucleosides C4 {\textquoteleft}-epi-DNA, Antisense Oligonucleotide}, issn = {1525-7770}, doi = {10.1080/15257770.2016.1202963}, author = {Bagmare, Seema and Puranik, Vedavati G. and Fernandes, Moneesha and Kumar, Vaijayanti A.} } @article { ISI:000377424600004, title = {Efficient cellular entry of (r-x-r)-type carbamate-plasmid DNA complexes and its implication for noninvasive topical DNA delivery to skin}, journal = {Molecular Pharmaceutics}, volume = {13}, number = {6}, year = {2016}, month = {JUN}, pages = {1779-1790}, publisher = {AMER CHEMICAL SOC}, address = {1155 16TH ST, NW, WASHINGTON, DC 20036 USA}, abstract = {

Arginine-rich cell penetrating peptides are powerful tools for in vitro as well as in vivo delivery of a wide plethora of biomolecules. However, presence of consecutive arginine residues leads to enhanced amenability for proteolytic degradation as well as steric hindrances for membrane interactions which compromise its bioavailability. In order to overcome these limitations we previously reported a safe and stable octaarginine based oligomer, i.e., (r-x-r)4-carbamate, where the backbone amide linkages were replaced by carbamate linkages and 6-aminohexanoic acid based spacer moieties were incorporated for better flexibility, hydrophobicity, optimal spacing of guanidinium groups, and protection against proteolytic cleavage; resulting in improved transfection efficiency over its amide counterpart. In the present work we have investigated the mechanism behind this enhanced transfection efficiency and, based on our observations, demonstrate how the synergistic effect of rationalized oligomer designing, complex characteristics, and cell type contributes to overall effective intracellular delivery. Our results indicate that the (r-x-r)4-carbamate plasmid DNA complexes primarily utilize lipid raft dependent pathway of cellular entry more than other pathways, and this possibly facilitates their increased entry in the lipid raft rich milieu of skin cells. We also emphasize the utility of oligomer (r-x-r)4-carbamate as an efficient carrier for topical delivery of nucleic acids in skin tissue. This carrier can be utilized for safe, efficient, and noninvasive delivery of therapeutically relevant macromolecular hydrophilic cargo like nucleic acids to skin.

}, keywords = {Cell penetrating peptides, endocytosis, nucleic acid delivery, skin penetration, transfection}, issn = {1543-8384}, doi = {10.1021/acs.molpharmaceut.5b00915}, author = {Vij, Manika and Natarajan, Poornemaa and Yadav, Amit K. and Patil, Kiran M. and Pandey, Tanuja and Gupta, Nidhi and Santhiya, Deenan and Kumar, Vaijayanti A. and Fernandes, Moneesha and Ganguli, Munia} } @article {45635, title = {Evolution of specific 3 {\textquoteleft}-5 {\textquoteleft}-linkages in RNA in pre-biotic soup: a new hypothesis}, journal = {Organic \& Biomolecular Chemistry}, volume = {14}, year = {2016}, month = {NOV}, pages = {10123-10133}, type = {Article}, abstract = {

This article reviews the different possibilities towards progression of the formation of DNA/RNA in the chemical world, before life, in enzyme-free conditions. The advent of deoxyribo- and ribopentose-sugars, nucleosides, nucleotides and oligonucleotides in the prebiotic soup is briefly discussed. Further, the formation of early single stranded oligomers, base-pairing possibilities and information transfer based on the stability parameters of the derived duplexes is reviewed. Each theory has its own merits and demerits which we have elaborated upon. Lastly, using clues from this literature, a possible explanation for the specific 3{\textquoteright}-5{\textquoteright}-linkages in RNA is proposed.

}, issn = {1477-0520}, doi = {10.1039/c6ob01796g}, author = {Kumar, Vaijayanti A.} } @article {45641, title = {Inhibition of miR-21 by 3 {\textquoteleft}/5 {\textquoteleft}-serinyl-capped 2 {\textquoteleft}-O-Methyl RNA Interspersed with 2 {\textquoteleft}-O-(2-Amino-3-Methoxypropyl) uridine units}, journal = {Nucleic Acid Therapeutics}, volume = {26}, year = {2016}, month = {OCT}, pages = {327-334}, type = {Article}, abstract = {

miRNAs are highly conserved class of small ncRNAs whose involvement in human pathophysiologies is extensively investigated. MiR-21 is a well established oncogenic miRNA whose deregulation plays a significant role in onset and progression of cancer. The need of novel approaches to downregulate miR-21 is rapidly expanding. Potent inhibition of miR-21 is achieved by chemically modified 2-O-methyl RNA oligonucleotide. The serinol capping at 3 and 5ends and the interspersed 2-O-(R-2-amino-3-methoxypropyl) uridine units enhance the nuclease resistance and efficacy of 2-O-methyl RNA for the inhibition of miR-21. This represents a simple and novel modification for developing oligonucleotide-based therapeutics.

}, keywords = {antagomirs, cancer, microRNA, noncoding RNA, oligonucleotides}, issn = {2159-3337}, doi = {10.1089/nat.2015.0591}, author = {Nahar, Smita and Kotikam, Venubabu and Kumar, Vaijayanti A. and Maiti, Souvik} } @article {45703, title = {Critical role of select peptides in the loop region of G-rich PNA in the preferred G-quadruplex topology and stability}, journal = {Tetrahedron}, volume = {73}, year = {2017}, month = {MAR}, pages = {1534-1540}, type = {Article}, abstract = {

An uncharged PNA 15mer sequence formed unimolecular antiparallel G-quadruplex similar to that observed for DNA-TBA. Replacement of {\textquoteleft}tt{\textquoteright} loop regions by peptides which induce helices or turns were found to have unpresidented effect on the quadruplex topology and stability. This study opens up a completely new strategy of utilizing G-quadruplex formation to display the array of functional groups in the three dimensional space thus creating a possibility of getting closer to the dream of designed peptides with three dimensional structures as observed in catalytic protein folds. (C) 2017 Elsevier Ltd. All rights reserved.

}, keywords = {ESI-MS study, G-quadruplex, Peptide nucleic acid, topology}, issn = {0040-4020}, doi = {10.1016/j.tet.2017.01.055}, author = {Bose, Tanaya and Kumar, Vaijayanti A.} } @article {44357, title = {Favorable 2 {\textquoteright}-substitution in the loop region of a thrombin-binding DNA aptamer}, journal = {Bioorganic \& Medicinal Chemistry Letters}, volume = {28}, year = {2018}, month = {JUN}, pages = {1765-1768}, type = {Article}, abstract = {Simple 2{\textquoteright}-OMe-chemical modification in the loop region of the 15mer G-rich DNA sequence GGTTGGTGTGGTTGG is reported. The G-quadruplex structure of this thrombin-binding aptamer (TBA), is stabilized by single modifications (T -> 2{\textquoteright}-OMe-U), depending on the position of the modification. The structural stability also renders significantly increased inhibition of thrombin-induced fibrin polymerization, a process closely associated with blood-clotting. (C) 2018 Elsevier Ltd. All rights reserved.}, doi = {10.1016/j.bmcl.2018.04.027}, author = {Awachat, Ragini and Wagh, Atish A. and Aher, Manisha and Fernandes, Moneesha and Kumar, Vaijayanti A.} } @article {46909, title = {Influence of fluorine substitution on the molecular conformation of 3 {\textquoteleft}-deoxy-3 {\textquoteleft}-fluoro-5-methyluriaine}, journal = {Acta Crystallographica Section C-Structural Chemistry}, volume = {76}, year = {2020}, month = {APR}, pages = {346+}, type = {Article}, abstract = {

{Fluorine substitutions on the furanose ring of nucleosides are known to strongly influence the conformational properties of oligonucleotides. In order to assess the effect of fluorine on the conformation of 3{\textquoteright}-deoxy-3{\textquoteright}-fluoro-5-methyluridine (T-R(F)), C-10 H13FN2O5, we studied its stereochemistry in the crystalline state using X-ray crystallography. The compound crystallizes in the chiral orthorhombic space group P2(1)2(1)2(1) and contains two symmetry-independent molecules (A and B) in the asymmetric unit. The furanose ring in molecules A and B adopts conformations between envelope (E-2, 2{\textquoteright}-endo

}, keywords = {crystal structure, fluoro nucleoside, pseudorotation parameter, sugar puckering, uridine}, issn = {2053-2296}, doi = {10.1107/S2053229620003083}, author = {Aher, Manisha N. and Erande, Namrata D. and Kumar, Vaijayanti A. and Fernandes, Moneesha and Gonnade, Rajesh G.} } @article {46999, title = {Methoxymethyl threofuranosyl thymidine (4 {\textquoteleft}-MOM-TNA-T) at the T7 position of the thrombin-binding aptamer boosts anticoagulation activity, thermal stability, and nuclease resistance}, journal = {ACS Omega}, volume = {5}, year = {2020}, month = {JAN }, pages = {498-506}, type = {Article}, abstract = {

The synthesis of 4{\textquoteright}-methoxymethyl threofuranosyl (4{\textquoteright}-MOM-TNA) thymidine and derived oligomers of the G-rich thrombin-binding aptameric (TBA) sequence is reported. The G-quadruplex stability, anticoagulation activity, and the enzymatic stability of these oligomers bearing the 2{\textquoteright}-3{\textquoteright}-phosphodiester backbone as single substitutions in the loop regions are studied. Amongst all the oligomers, TBA-7T bearing the 4{\textquoteright}-MOM-TNA unit at the T7 position formed a quadruplex with the highest thermal stability. It also resulted in enhanced anticlotting activity that allowed a one-third reduction in the dose, relative to TBA. Further, TBA-7T exhibited enhanced nuclease resistance properties to both endo- and exonucleases.

}, issn = {2470-1343}, doi = {10.1021/acsomega.9b03042}, author = {Varada, Manojkumar and Aher, Manisha and Erande, Namrata and Kumar, Vaijayanti A. and Fernandes, Moneesha} }