01228nas a2200205   4500008004100000022001400041245008900055210006900144260011000213300001400323490000700337520040000344100001700744700002200761700003100783700002600814700003500840700002800875856011900903       2015                        eng d  a1477-052000aConformational modulation of peptides using beta-amino benzenesulfonic acid ((S)Ant)0 aConformational modulation of peptides using betaamino benzenesul  aTHOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLANDbROYAL SOC CHEMISTRYcDEC  a2087-20910 v133 a<p>This communication describes the utility of a conformationally restricted aromatic beta-amino acid (2-aminobenzenesulfonic acid, (S)Ant) inducing various folding interactions in short peptides. Sandwiching (S)Ant between diverse amino acid residues was shown to form robust folded architectures featuring a variety of H-bonded networks, suggesting its utility in inducing peptide folding.</p>1 aPriya, Gowri1 aKotmale, Amol, S.1 aChakravarty, Debamitra, K.1 aPuranik, Vedavati, G.1 aRajamohanan, Pattuparambil, R.1 aSanjayan, Gangadhar, J.  uhttps://library.ncl.res.in/content/conformational-modulation-peptides-using-beta-amino-benzenesulfonic-acid-sant-003043nas a2200229   4500008004100000022001400041245016600055210006900221260011000290300001400400490000600414520208700420100002302507700003102530700002402561700001702585700001602602700002402618700002602642700002202668856012302690       2016                        eng d  a2046-206900aComparative study of dG affinity vs. DNA methylation modulating properties of side chain derivatives of procainamide: insight into its DNA hypomethylating effect0 aComparative study of dG affinity vs DNA methylation modulating p  aTHOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLANDbROYAL SOC CHEMISTRYcJAN  a5350-53580 v63 a<p>Procainamide derivatives have been synthesized to investigate the role of side chains in modulating the DNA methylation level in cancer cells and gain insight into its mechanism of action. The synthesized derivatives comprised of flexible (dimethyl), constrained (pyrrolidine, piperidine, morpholine) and planar aromatic (pyridine, phenyl) side chain motifs. The affinity of procainamide and its derivatives towards the deoxyguanosine (dG) base in neutral form has been assessed by performing Differential Pulse Voltammetry (DPV) under physiological conditions. Further, molecular docking with hemimethylated CpG rich DNA acquired from an active mDNMT-1-DNA (PDB ID-4DA4) crystal structure, reveals their preferential non-covalent interaction with dG nucleobase in the intercalation cavity of the minor groove. Differential affinity of the derivatives to dG base in neutral and bound forms (DNA) is correlated with their DNA methylation modulating properties at sub-lethal concentrations. Among all the derivatives, a compound with an aromatic phenyl side chain (1) has shown a highest binding affinity for dG nucleobase in neutral form as well as for partially denatured CpG rich DNA which is attributed to the formation of p/p stacking interaction in addition to N-H/O hydrogen bonding with the pyrimidine ring of dG base. It also shows the highest cytotoxicity and global hypomethylation at a sub-lethal level in the MCF-7 cancer cell line compared to other derivatives and procainamide. A docking study has also illustrated the plausible structural basis of DNA methylation modulating a property of procainamide. Strong association of procainamide with dG bases of partially denatured CpG rich DNA via H-bonding and other non-covalent interactions may alter the active topology of DNA required by the DNA-binding regulatory proteins (e. g. DNMT-1) which is validated by a DNMT-1 inhibition assay. This systematic investigation leads to a new potent alternative to procainamide being found and gives a plausible insight into the DNA hypomethylating effect of procainamide.</p>1 aGawade, Rupesh, L.1 aChakravarty, Debamitra, K.1 aDebgupta, Joyashish1 aSangtani, E.1 aNarwade, S.1 aGonnade, Rajesh, G.1 aPuranik, Vedavati, G.1 aDeobagkar, D., D.  uhttps://library.ncl.res.in/content/comparative-study-dg-affinity-vs-dna-methylation-modulating-properties-side-chain-0