The ability or (S)-α-methylproline(α-MePro) to stabilise reverse-turn conformations in the peptide hormone bradykinin (BK = Arg1-Pro2-Pro3-Gly4I-Phe5-Ser6-Pro7-Phe8-Arg9) has been investigated. Two BK analogues containing α-MePro at position 3 or position 7 were synthesised and their conformations in aqueous solution investigated by NMR spectroscopy. Whereas BK is largely disordered on the NMR time scale both analogues showed ROE connectivities in 2D-ROESY spectra indicative of reverse-turn conformations at both Pro2-Phe5 and Ser6-Arg9, whose formation appears to be cooperative. Some potential applications of α-MePro as a reverse-turn mimetic in the construction of synthetic peptide libraries is discussed.
