NUCLEAR MAGNETIC-RESONANCE CONFORMATIONAL STUDIES ON THE CHEMOTACTIC TRIPEPTIDE FORMYL-L-METHIONYL-L-LEUCYL-L-PHENYLALANINE - SMALL BETA-SHEET

Previous work by several groups has shown that the combination of spin-spin coupling constants and spectral density components (derived from spin-lattice relaxation and/or nuclear Overhauser measurements) may aid in the task of conformational determination of peptides in solution. The peptide formyl-L-methionyl-L-leucyl-L-phenylalanine, which is a potent specific chemotactic agent for leukocytes, was used here. 3JNHCH coupling constants are consistent with a high degree of rigidity in the peptide backbone in solution. 2H isotopic substitution in combination with relaxation data taken at different Larmor frequencies enables spectral density, and thus conformational, information to be obtained. Side-chain conformations for this molecule mirror, in some aspects, those found in the solid state for other peptides containing the same residues. Temperature dependence of amide chemical shifts does not have direct implication concerning the existence of intramolecular H bonds in peptides. A family of conformations is proposed which appear to interchange rapidly on the NMR time scale and are characterized by a distribution of side-chain rotamers. The basic backbone conformation is, or closely approximates, a small .beta. antiparallel pleated sheet and as such suggests a possible mode of receptor-chemotactic peptide interaction.