Synthesis of new modified truncated peptides and inhibition of glycogen phosphorylase. Export

@article{citeulike:5899177, abstract = {The first solution state structural analysis (NMR) of the C-terminal sequence of human G(L) that binds to glycogen phosphorylase a (GPa), PEWPSYLGYEKLGPYY-NH(2) (1), showed it to be in a random coil conformation. This was supported by molecular dynamics simulation (modelled in solution) using NAMD 2.6. The conformational ambiguity of the peptide makes the structural arrangement of the peptide (and internal residues) strongly dependent on the environment. Thirteen tetra-peptide fragments of the C-terminal sequence, YEKLG-NH(2), and the corresponding tri- and di-peptide sequences were used in a fragment screen against GPa. Compound 2 (H-GPYY-NH(2)) did not give an IC(50) value, whereas PEWPSYLGYEKLGPYY-NH(2) (1) displayed an IC(50) of 34 microM against GPa. Truncated peptides derived from 1, (EKL-NH(2), EKLG-NH(2), and AcEKNH(2)) inhibited GPa (21\%, 32\%, 63\%, respectively at 22 mM). These studies suggest key residues within the peptide chain have additional molecular interactions with GPa. The interaction of intra-sequence residues in combination with the terminal residues of PEWPSYLGYEKLGPYY with GPa may form the basis for the design of new inhibitors of GPa.}, author = {Schweiker, Stephanie S. and Loughlin, Wendy A. and Brown, Christopher L. and Pierens, Gregory K.}, citeulike-article-id = {5899177}, citeulike-linkout-0 = {http://dx.doi.org/10.1002/psc.1140}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19399818}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19399818}, doi = {10.1002/psc.1140}, issn = {1099-1387}, journal = {Journal of peptide science : an official publication of the European Peptide Society}, keywords = {docking, peptide}, month = {June}, number = {6}, pages = {442--450}, posted-at = {2009-10-06 16:15:43}, priority = {2}, title = {Synthesis of new modified truncated peptides and inhibition of glycogen phosphorylase.}, url = {http://dx.doi.org/10.1002/psc.1140}, volume = {15}, year = {2009} }

TY - JOUR ID - citeulike:5899177 L3 - citeulike-article-id:5899177 N2 - The first solution state structural analysis (NMR) of the C-terminal sequence of human G(L) that binds to glycogen phosphorylase a (GPa), PEWPSYLGYEKLGPYY-NH(2) (1), showed it to be in a random coil conformation. This was supported by molecular dynamics simulation (modelled in solution) using NAMD 2.6. The conformational ambiguity of the peptide makes the structural arrangement of the peptide (and internal residues) strongly dependent on the environment. Thirteen tetra-peptide fragments of the C-terminal sequence, YEKLG-NH(2), and the corresponding tri- and di-peptide sequences were used in a fragment screen against GPa. Compound 2 (H-GPYY-NH(2)) did not give an IC(50) value, whereas PEWPSYLGYEKLGPYY-NH(2) (1) displayed an IC(50) of 34 microM against GPa. Truncated peptides derived from 1, (EKL-NH(2), EKLG-NH(2), and AcEKNH(2)) inhibited GPa (21%, 32%, 63%, respectively at 22 mM). These studies suggest key residues within the peptide chain have additional molecular interactions with GPa. The interaction of intra-sequence residues in combination with the terminal residues of PEWPSYLGYEKLGPYY with GPa may form the basis for the design of new inhibitors of GPa. IS - 6 JF - Journal of peptide science : an official publication of the European Peptide Society SN - 1099-1387 EP - 450 TI - Synthesis of new modified truncated peptides and inhibition of glycogen phosphorylase. VL - 15 SP - 442 KW - docking KW - peptide AU - Schweiker, Stephanie AU - Loughlin, Wendy AU - Brown, Christopher AU - Pierens, Gregory PY - 2009/06// UR - http://dx.doi.org/10.1002/psc.1140 ER -