For some years synthetic peptides corresponding to the C-terminal sequence of Ga 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 A2A receptor/Gs protein system. We have synthesised a series of 11-mer peptides from the Gas Cterminus in which residue at position-2 (Leu393) has been alternatively substituted with amino acids having different physicochemical properties. The aim of our work was to probe the role played by Leu393 in the receptor/Gas 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 Gas 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.

A structure – activity relationship study on position –2 of the Gas C-terminal peptide able to inhibit Gs activation by A2A adenosine receptor / GRIECO P.; ALBRIZIO P.; D'URSI A.M.; GIUSTI L.; MAZZONI M.; NOVELLINO E.; P. ROVERO. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - STAMPA. - 38:(2003), pp. 13-18. [10.1016/S0223-5234(02)00010-7]

A structure – activity relationship study on position –2 of the Gas C-terminal peptide able to inhibit Gs activation by A2A adenosine receptor

ROVERO, PAOLO
2003

Abstract

For some years synthetic peptides corresponding to the C-terminal sequence of Ga 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 A2A receptor/Gs protein system. We have synthesised a series of 11-mer peptides from the Gas Cterminus in which residue at position-2 (Leu393) has been alternatively substituted with amino acids having different physicochemical properties. The aim of our work was to probe the role played by Leu393 in the receptor/Gas 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 Gas 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.
2003
38
13
18
GRIECO P.; ALBRIZIO P.; D'URSI A.M.; GIUSTI L.; MAZZONI M.; NOVELLINO E.; P. ROVERO
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/312891
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