For some years synthetic peptides corresponding to the C-terminal sequence of Galpha proteins represented an useful tool to study the molecular mechanism of the interaction between these proteins and the G protein coupled receptors. Recently, we have focused our attention on the study of the A(2A) receptor-G(s) protein system. We have synthesised a series of 11-mer peptides from the Galpha(s) C-terminus in which residue at position-2 (Leu(393)) has been alternatively substituted with amino acids having different physicochemical properties. The aim of our work was to probe the role played by Leu(393) in the receptor/Galpha(s) interaction. All synthetic peptides were tested for their ability to affect the adenylyl cyclase activity stimulated by agonist activation of A2A adenosine receptors. Our data point out a relevant role played by the side chain of this residue for a correct G protein/receptor coupling, even though the presence of other residues at position-2 of Galpha(s) C-terminus is tolerated. Furthermore, molecular dynamics calculations on the peptides having greater activity show a correlation between the spatial arrangement of the side chain of residue at position-2 and biological activity of synthetic peptides. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved.
|Autori interni:||MAZZONI, MARIA ROSA|
|Autori:||Grieco P; Albrizio S; D'Ursi A; Giusti L; Mazzoni M; Novellino E; Rovero P|
|Titolo:||A structure-activity relationship study on position-2 of the G alpha(s) C-terminal peptide able to inhibit G(s) activation by A(2A) adenosine receptor|
|Anno del prodotto:||2003|
|Digital Object Identifier (DOI):||10.1016/S0223-5234(02)00010-7|
|Appare nelle tipologie:||1.1 Articolo in rivista|