The conformational bias of F((2R,3S)-cyclo-M)RFa induced by the cis-2,3-methanomethionine residue

The objective of this work was to study conformational biases attributable to a cis-2,3-methanomethionine isomer substituted in a model sequence, FMRFa, and to compare them with previous studies of trans-2,3-methanomethionine stereoisomers in the same environment. Consequently, F((2R,3S)-cyclo-M)RFa was prepared via solid phase synthesis, and solutions of this material were examined by NMR and CD spectroscopies. These spectral studies were complemented by molecular simulations. These computational studies indicated gamma- and beta-turn structures were favored; however, the experimental data are consistent with only the gamma-turn structure. Overall, this work. and previous research indicates that both cis- and trans-2,3-methanomethionine stereoisomers tend to impart a conformational preference for gamma-turns when substituted for methionine in FMRFa. It is proposed that this phenomenon is indirectly due to widening of the N-C-alpha-CO bond angle by the cyclopropane and might therefore be observed for 2,3-methanomethionine residues in other sequences.