CONFORMATIONAL STUDIES ON PEPTIDES WITH UNUSUAL AMINO-ACID SIDE-CHAINS - THE TRIFLUOROMETHYL GROUP

High-level ab initio MO calculations on the model compound N-acetyl-2- trifluoromethylglycyl-N'-methylamide as a basic peptide unit for an am ino acid with a trifluoromethyl side-chain employing the 6-31G and 3- 21G basis sets and considering the correlation energy by the MP2 metho d were performed. The influence of the trifluoromethyl group on the co nformation possibilities of this structure element was determinated in comparison with the corresponding alanine and valine derivatives in t he gas phase and in solution. The conformers were characterized by vib ration analysis. The solvent influence was estimated using a polarizab le continuum model incorporated into the ab initio procedure. The conf ormation dynamics in the various states of matter was studied by molec ular dynamics simulations based on the empirical GROMOS force field. M ost striking is the preference of the C-5 conformation over the C-7eq form contrary to the corresponding alanine and valine derivative. Thus , a stronger tendency to form beta-structures can be expected for amin o acids with a trifluoromethyl side-chain. Again in contrast to the al anine derivative, the helical alpha(R) conformation is not realized in solution.