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Structural determinants of unexpected agonist activity in a retro‐peptide analogue of the SDF‐1α N‐terminus
Author(s) -
Palladino Pasquale,
Tizzano Barbara,
Pedone Carlo,
Ragone Raffaele,
Rossi Filomena,
Saviano Gabriella,
Tancredi Teodorico,
Benedetti Ettore
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.07.100
Subject(s) - agonist , peptide , receptor , extracellular , phosphorylation , chemistry , microbiology and biotechnology , n terminus , biological activity , kinase , signal transduction , biochemistry , biology , peptide sequence , in vitro , gene
We have synthesised two retro‐peptide analogues of the stromal cell derived growth factor 1 (SDF‐1α) 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‐1α 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 β‐β‐type turn motif centred on Phe 4 –Phe 5 .