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001-es BibID:	BIBFORM003564
Első szerző:	Anagnostou, Eleni
Cím:	Crystallographic studies on two bioisosteric analogues, N-acetyl-beta-D-glucopyranosylamine and N-trifluoroacetyl-beta-D-glucopyranosylamine, potent inhibitors of muscle glycogen phosphorylase / Anagnostou E., Kosmopoulou N., Chrysina E.D., Leonidas D.D., Hadjiloi T., Tiraidis C., Zographos S.E., Györgydeák Z., Somsák L., Docsa T., Gergely P., Kolisis F.N., Oikonomakos N.G.
Dátum:	2006
Megjegyzések:	Structure-based inhibitor design has led to the discovery of a number of potent inhibitors of glycogen phosphorylase b (GPb), N-acyl derivatives of beta-D-glucopyranosylamine, that bind at the catalytic site of the enzyme. The first good inhibitor in this class of compounds, N-acetyl-beta-D-glucopyranosylamine (NAG) (Ki = 32 nM), has been previously characterized by biochemical, biological and crystallographic experiments at 2.3 A resolution. Bioisosteric replacement of the acetyl group by trifluoroacetyl group resulted in an inhibitor, N-trifluoroacetyl-beta-D-glucopyranosylamine (NFAG), with a Ki = 75 nM. To elucidate the structural basis of its reduced potency, we determined the ligand structure in complex with GPb at 1.8 A resolution. To compare the binding mode of N-trifluoroacetyl derivative with that of the lead molecule, we also determined the structure of GPb?NAG complex at a higher resolution (1.9 A). NFAG can be accommodated in the catalytic site of T-state GPb at approximately the same position as that of NAG and stabilize the T-state conformation of the 280s loop by making several favourable contacts to Asn284 of this loop. The difference observed in the Ki values of the two analogues can be interpreted in terms of subtle conformational changes of protein residues and shifts of water molecules in the vicinity of the catalytic site, variations in van der Waals interaction, and desolvation effects.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban type 2 diabetes glycogen phosphorylase N-acetyl-beta-D-glucopyranosylamine N-trifluoroacetyl-beta-D-glucopyranosylamine bioisosteric inhibition X-ray crystallography
Megjelenés:	Bioorganic and Meidicnal Chemistry 14 : 1 (2006), p. 181-189. -
További szerzők:	Kosmopoulou, Magda N. Chrysina, Evangelia D. Leonidas, Demetres D. Hadjiloi, Theodoros Tiraidis, Costantinos Zographos, Spyros E. Györgydeák Zoltán (1942-2005) (vegyész) Somsák László (1954-) (vegyész) Docsa Tibor (1975-) (vegyész, biokémikus) Gergely Pál (1947-) (biokémikus) Kolisis, Fragiskos N. Oikonomakos, George N.
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat DOI
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001-es BibID:	BIBFORM003576
Első szerző:	Chrysina, Evangelia D.
Cím:	Kinetic and crystallographic studies on 2-(beta-D-glucopyranosyl)-5-methyl-1, 3, 4-oxadiazole, -benzothiazole, and -benzimidazole, inhibitors of muscle glycogen phosphorylase b. Evidence for a new binding site / Chrysina E. D., Kosmopoulou M. N., Tiraidis C., Kardakaris R., Bischler N., Leonidas D. D., Hadady Zs., Somsák L., Docsa T., Gergely P., Oikonomakos N. G.
Dátum:	2005
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban type 2 diabetes glycogen phosphorylase beta-D-glucopyranosyl analogs inhibition X-ray crystallography
Megjelenés:	Protein Science. - 14 : 4 (2005), p. 873-888. -
További szerzők:	Kosmopoulou, Magda N. Tiraidis, Costantinos Kardakaris, Rozina Bischler, Nicolas Leonidas, Demetres D. Hadady Zsuzsa (1977-) (vegyész) Somsák László (1954-) (vegyész) Docsa Tibor (1975-) (vegyész, biokémikus) Gergely Pál (1947-) (biokémikus) Oikonomakos, Nikos G.
Internet cím:	elektronikus változat
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001-es BibID:	BIBFORM006384
Első szerző:	Somsák László (vegyész)
Cím:	New inhibitors of glycogen phosphorylase as potential antidiabetic agents / L. Somsák, K. Czifrák, M. Tóth, É. Bokor, E. D. Chrysina, K.-M. Alexacou, J. M. Hayes, C. Tiraidis, E. Lazoura, D. D. Leonidas, S. E. Zographos, N. G. Oikonomakos
Dátum:	2008
ISSN:	0929-8673
Megjegyzések:	The protein glycogen phosphorylase has been linked to type 2 diabetes, indicating the importance of this target to human health. Hence, the search for potent and selective inhibitors of this enzyme, which may lead to antihyperglycaemic drugs, has received particular attention. Glycogen phosphorylase is a typical allosteric protein with five different ligand binding sites, thus offering multiple opportunities for modulation of enzyme activity. The present survey is focused on recent new molecules, potential inhibitors of the enzyme. The biological activity can be modified by these molecules through direct binding, allosteric effects or other structural changes. Progress in our understanding of the mechanism of action of these inhibitors has been made by the determination of high-resolution enzyme inhibitor structures (both muscle and liver). The knowledge of the three-dimensional structures of protein-ligand complexes allows analysis of how the ligands interact with the target and has the potential to facilitate structure-based drug design. In this review, the synthesis, structure determination and computational studies of the most recent inhibitors of glycogen phosphorylase at the different binding sites are presented and analyzed.
Tárgyszavak:	Természettudományok Kémiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban glycogen phosphorylase inhibitor type 2 diabetes structure-based drug design antidiabetic agent
Megjelenés:	Current Medicinal Chemistry. - 15 : 28 (2008), p. 2933-2983. -
További szerzők:	Czifrák Katalin (1978-) (vegyész) Tóth Marietta (1974-) (vegyész) Bokor Éva (1982-) (vegyész) Chrysina, Evangelia D. Alexacou, Kyra-Melinda Hayes, Joseph M. Tiraidis, Costantinos Lazoura, E. Leonidas, Demetres D. Zographos, Spyros E. Oikonomakos, George N.
Internet cím:	elektronikus változat
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