Synthesis,biological activity,conformational analysis by NMR and molecular modeling of N-formyl-L-Met-L-Pro-L-Phe-OMe,a praline analogue of the chemotactic peptide N-formyl-L-Met-L-Leu-L-Phe-OH |
| |
Authors: | H. DUGAS,M. LAROCHE,M. PTAK,H. LABB |
| |
Affiliation: | H. DUGAS,M. LAROCHE,M. PTAK,H. LABBÉ |
| |
Abstract: | The tripeptide N-formyl-Met-Pro-Phe-OMe (f-MPF-OMe), an analogue of the signal peptide N-formyl-Met-Leu-Phe-OH (f-MLF-OH), was synthesized and its chemotactic activity evaluated; it showed no activity in either superoxide production or calcium mobility with human neutrophils. However, the corresponding acid f-MPF-OH retained about 25% activity in the production of superoxide. The conformation of the f-MPF-OMe analogue was evaluated by NMR spectroscopy and molecular simulation and shown to predominate in a γ-turn with a hydrogen bond between Met CO and Phe NH. Since this analogue is not chemotactic, it is suggested that for recognition the receptor prefers a peptide with a flexible backbone, favoring an extended conformation in the binding site. |
| |
Keywords: | chemotactic activity chemotactic peptide molecular mechanics simulation Monte Carlo method N-formyl-Met-Pro-Phe-OMe peptide conformation peptide synthesis |
|
|