Abstract We have synthesised two retro-peptide analogues of the stromal cell derived growth factor 1 (SDF-1a) segment known to be critical for CXCR4 receptor binding, corresponding to the sequences HSEFFRCPCRFFESH and HSEFFRGGGRFFESH. We have assayed the ability of these peptides to activate extracellular signal-regulated kinase 1/2 phosphorylation in cells over expressing the SDF-1a receptor, finding that the first variant was able to serve as an agonist of CXCR4, whereas the second one was inactive. Finally, by comparing representative solution structures of the two peptides, we have found that the biological response of HSEFFRCPCRFFESH may be ascribed to a b-b-type turn motif centred on Phe4–Phe5.
Structural determinants of unexpected agonist activity in a retropeptide analogue of the SDF-1α N-terminus
SAVIANO, Gabriella;
2005-01-01
Abstract
Abstract We have synthesised two retro-peptide analogues of the stromal cell derived growth factor 1 (SDF-1a) segment known to be critical for CXCR4 receptor binding, corresponding to the sequences HSEFFRCPCRFFESH and HSEFFRGGGRFFESH. We have assayed the ability of these peptides to activate extracellular signal-regulated kinase 1/2 phosphorylation in cells over expressing the SDF-1a receptor, finding that the first variant was able to serve as an agonist of CXCR4, whereas the second one was inactive. Finally, by comparing representative solution structures of the two peptides, we have found that the biological response of HSEFFRCPCRFFESH may be ascribed to a b-b-type turn motif centred on Phe4–Phe5.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
