02138nas a2200157 4500008004100000022001400041245007000055210006900125260011100194300001200305490000600317520151000323100002601833700002401859856009701883 2007 eng d a1568-026600aStructure-editing of nucleic acids for selective targeting of RNA0 aStructureediting of nucleic acids for selective targeting of RNA aEXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATESbBENTHAM SCIENCE PUBL LTDcJAN a715-7260 v73 a

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.

1 aKumar, Vaijayanti, A.1 aGanesh, Krishna, N. uhttps://library.ncl.res.in/content/structure-editing-nucleic-acids-selective-targeting-rna-001691nas a2200193 4500008004100000022001400041245010700055210006900162260010600231300001400337490000700351520088300358653002701241653001301268653003601281100002201317700002601339856013201365 2013 eng d a0040-402000aSynthesis and properties of 2 `-O-[R- and S-(2-amino-3-methoxy)propyl] (R-AMP and S-AMP) nucleic acids0 aSynthesis and properties of 2 OR and S2amino3methoxypropyl RAMP  aTHE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLANDbPERGAMON-ELSEVIER SCIENCE LTDcAUG a6404-64080 v693 a

Substitution at 2'-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'-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.

10aAntisense therapeutics10aMOE-AONs10aPositively charged ON analogues1 aKotikam, Venubabu1 aKumar, Vaijayanti, A. uhttps://library.ncl.res.in/content/synthesis-and-properties-2-o-r-and-s-2-amino-3-methoxypropyl-r-amp-and-s-amp-nucleic-acids-001456nas a2200193 4500008004100000022001400041245018200055210006900237260011000306300001200416490000700428520057600435100002401011700002201035700002401057700002401081700002601105856013101131 2013 eng d a1477-052000aSynthesis and structural studies of S-type/N-type-locked/frozen nucleoside analogues and their incorporation in RNA-selective, nuclease resistant 2 `-5 ` linked oligonucleotides0 aSynthesis and structural studies of StypeNtypelockedfrozen nucle aTHOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLANDbROYAL SOC CHEMISTRYcNOV a746-7570 v113 a

2'-endo locked or frozen (S-type)/3'-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'-5' isoDNA oligonucleotides (ON) were synthesized using these modified nucleoside analogues and UV-T-m studies of the resultant 2'-5' 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.

1 aErande, Namrata, D.1 aGunjal, Anita, D.1 aFernandes, Moneesha1 aGonnade, Rajesh, G.1 aKumar, Vaijayanti, A. uhttps://library.ncl.res.in/content/synthesis-and-structural-studies-s-typen-type-lockedfrozen-nucleoside-analogues-and-their-001347nas a2200217 4500008004100000022001400041245018500055210006900240260010600309300001400415490000700429520039500436653002700831653002600858653003200884100001900916700002300935700002000958700002600978856012501004 2013 eng d a0040-402000aSynthesis 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 acids0 aSynthesis of all four nucleosidebased betaamino acids as protect aTHE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLANDbPERGAMON-ELSEVIER SCIENCE LTDcJAN a1210-12160 v693 a

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'-3'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.

10aAntisense therapeutics10aNeutral DNA analogues10aNucleoside-beta amino acids1 aBagmare, Seema1 aVarada, Manojkumar1 aBanerjee, Anjan1 aKumar, Vaijayanti, A. uhttps://library.ncl.res.in/content/synthesis-all-four-nucleoside-based-beta-amino-acids-protected-precursors-synthesis-001962nas a2200277 4500008004100000022001400041245018700055210006900242260010600311300001400417490000700431520083800438653001801276653003001294653002901324653003401353653002001387100002101407700002401428700001601452700002001468700002601488700001901514700002401533856012701557 2014 eng d a0960-894X00aSecond generation, arginine-rich (R-X `-R)(4)-type cell-penetrating alpha-omega-alpha-peptides with constrained, chiral omega-amino acids (X `) for enhanced cargo delivery into cells0 aSecond generation argininerich RX R4type cellpenetrating alphaom aTHE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLANDbPERGAMON-ELSEVIER SCIENCE LTDcSEP a4198-42020 v243 a

The syntheses of novel N-aminoalkyl proline-derived spacers (X') in polycationic (R-X'-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.

10a(R-X-R)-motif10aalpha-omega-alpha-Peptide10aCell-penetrating peptide10aConstrained chiral amino acid10aPeptidomimetics1 aPatil, Kiran, M.1 aNaik, Rangeetha, J.1 aVij, Manika1 aYadav, Amit, K.1 aKumar, Vaijayanti, A.1 aGanguli, Munia1 aFernandes, Moneesha uhttps://library.ncl.res.in/content/second-generation-arginine-rich-r-x-r4-type-cell-penetrating-alpha-omega-alpha-peptides01711nas a2200217 4500008004100000022001400041245012200055210006900177260010600246300001400352490000700366520086400373653003201237653001801269653000901287653000801296653001701304100001701321700002601338856012901364 2014 eng d a0968-089600aSimple molecular engineering of glycol nucleic acid: progression from self-pairing to cross-pairing with cDNA and RNA0 aSimple molecular engineering of glycol nucleic acid progression  aTHE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLANDbPERGAMON-ELSEVIER SCIENCE LTDcNOV a6227-62320 v223 a

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.

10aAcyclic chiral nucleic acid10aCross-pairing10aGCNA10aGNA10aSelf-pairing1 aBose, Tanaya1 aKumar, Vaijayanti, A. uhttps://library.ncl.res.in/content/simple-molecular-engineering-glycol-nucleic-acid-progression-self-pairing-cross-pairing-0