Crystal structure, conformation, and potential energy calculations of the chemotactic peptide N-formyl-L-Met-L-Leu-L-Phe-OMe.

The tripeptide N-formyl-L-Met-L-Leu-L-Phe-OMe (FMLP-OMe) crystallizes in the orthorhombic system, space group P 2(1)2(1)2(1), with the following unit-cell parameters: a = 21.727, b = 21.836, c = 5.133 A, Z = 4. The structure has been solved and refined to a final R of 0.068 for 1838 independent reflexions with I greater than 2 omega (I). The peptide backbone is folded at the Leu residue (phi L = -67.7, psi L = -49.1 degrees) without intramolecular hydrogen bonds. Considering each peptide plane, the Leu side-chain is oriented on the same side of that of the Phe residue and on the opposite side of that of the Met residue, respectively. The crystal conformation differs from all the other conformations proposed for FMLP-OMe and the anionic form of N-formyl-L-Met-L-Leu-L-Phe-OH (FMLP) in solution accounts for the amphiphilic character of the peptide, giving rise, through intermolecular hydrogen bonds, to a stacking of molecules which could be maintained in the aggregation states experimentally observed in solvents of low polarity. Intramolecular potential energy calculations have been carried out in order to compare the energies of the various backbone conformers.