00936nas a2200157 4500008004100000022001400041245015200055210006900207260011000276300001400386520018500400100001900585700002200604700002600626856012600652 2009 eng d a1359-734500aEffect of chirality of L/D-proline and prochiral glycine as the linker amino acid in five-atom linked thymidinyl-(alpha-aminoacid)-thymidine dimers0 aEffect of chirality of LDproline and prochiral glycine as the li aTHOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLANDbROYAL SOC CHEMISTRYcSEP a6646-66483 a

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.

1 aBagmare, Seema1 aD'Costa, Moneesha1 aKumar, Vaijayanti, A. uhttps://library.ncl.res.in/content/effect-chirality-ld-proline-and-prochiral-glycine-linker-amino-acid-five-atom-linked-002740nas a2200217 4500008004100000022001400041245015100055210006900206260007100275300001400346490000800360520189600368100001802264700001602282700001402298700001602312700002202328700002602350700001802376856012802394 2009 eng d a1520-610600aEffects for the incorporation of five-atom thioacetamido nucleic acid (TANA) backbone on hybridization thermodynamics and kinetics of DNA duplexes0 aEffects for the incorporation of fiveatom thioacetamido nucleic  a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcMAR a2944-29510 v1133 a

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 ``thioacetamido linkage'' (TANA) on thermodynamics of hybridization, binding kinetics, and conformation of a DNA duplex. The modification comprises of an extended five-atom amide (N3'-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.

1 aKaur, Harleen1 aArora, Amit1 aGogoi, K.1 aSolanke, P.1 aGunjal, Anita, D.1 aKumar, Vaijayanti, A.1 aMaiti, Souvik uhttps://library.ncl.res.in/content/effects-incorporation-five-atom-thioacetamido-nucleic-acid-tana-backbone-hybridization-001240nas a2200169 4500008004100000022001400041245006100055210005900116260011000175300001600285490000600301520059800307100002300905700002400928700002600952856009200978 2015 eng d a2046-206900aEne-nucleic acids: a different paradigm to DNA chemistry0 aEnenucleic acids a different paradigm to DNA chemistry aTHOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLANDbROYAL SOC CHEMISTRYcNOV a97824-978300 v53 a

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.

1 aVarada, Manojkumar1 aErande, Namrata, D.1 aKumar, Vaijayanti, A. uhttps://library.ncl.res.in/content/ene-nucleic-acids-different-paradigm-dna-chemistry-002799nas a2200313 4500008004100000022001400041245014200055210006900197260007100266300001400337490000700351520168200358653003002040653001602070653002602086653002102112653001702133100001602150700002502166700002002191700002102211700001902232700001702251700002102268700002602289700002402315700001902339856012702358 2016 eng d a1543-838400aEfficient cellular entry of (r-x-r)-type carbamate-plasmid DNA complexes and its implication for noninvasive topical DNA delivery to skin0 aEfficient cellular entry of rxrtype carbamateplasmid DNA complex a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcJUN a1779-17900 v133 a

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.

10aCell penetrating peptides10aendocytosis10anucleic acid delivery10askin penetration10atransfection1 aVij, Manika1 aNatarajan, Poornemaa1 aYadav, Amit, K.1 aPatil, Kiran, M.1 aPandey, Tanuja1 aGupta, Nidhi1 aSanthiya, Deenan1 aKumar, Vaijayanti, A.1 aFernandes, Moneesha1 aGanguli, Munia uhttps://library.ncl.res.in/content/efficient-cellular-entry-r-x-r-type-carbamate-plasmid-dna-complexes-and-its-implication01204nas a2200145 4500008004100000022001400041245008700055210006900142260000800211300001600219490000700235520068400242100002600926856010600952 2016 eng d a1477-052000aEvolution of specific 3 `-5 `-linkages in RNA in pre-biotic soup: a new hypothesis0 aEvolution of specific 3 5 linkages in RNA in prebiotic soup a ne cNOV a10123-101330 v143 a

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'-5'-linkages in RNA is proposed.

1 aKumar, Vaijayanti, A. uhttps://library.ncl.res.in/content/evolution-specific-3-5-linkages-rna-pre-biotic-soup-new-hypothesis