Structural determinants of unexpected agonist activity in a retro-peptide analogue of the SDF-1alpha N-terminus |
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Authors: | Palladino Pasquale Tizzano Barbara Pedone Carlo Ragone Raffaele Rossi Filomena Saviano Gabriella Tancredi Teodorico Benedetti Ettore |
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Affiliation: | Dipartimento delle Scienze Biologiche, CIRPeB, Università Federico II di Napoli, CNR, Italy. palladin@chemistry.unina.it |
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Abstract: | We have synthesised two retro-peptide analogues of the stromal cell derived growth factor 1 (SDF-1alpha) 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-1alpha 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 beta-beta-type turn motif centred on Phe(4)-Phe(5). |
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Keywords: | CALIBA, calibration of NOE distance constraints DYANA, dynamics algorithm for NMR applications ECL, enhanced chemiluminescence ERK1/2, extracellular signal-regulated kinases 1/2 MOLMOL, MOLecule analysis and MOLecule display SDF-1α, stromal cell derived growth factor 1 TSSA, torsion space simulated annealing |
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