Beta-turns induced in bradykinin by (S)-alpha-methylproline.
The ability of (S)-alpha-methylproline (alpha-MePro) to stabilise reverse-turn conformations in the peptide hormone bradykinin (BK = Arg1-Pro2-Pro3-Gly4-Phe5-Ser6-Pro7-Phe8-Arg9) has been investigated. Two BK analogues containing alpha-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 alpha-MePro as a reverse-turn mimetic in the construction of synthetic peptide libraries is discussed.
Welsh
J H
JH
Institute of Organic Chemistry, University of Zürich, Switzerland.
Zerbe
O
O
von Philipsborn
W
W
Robinson
J A
JA
D000595:Amino Acid Sequence; D001920:Bradykinin / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D011392:Proline / Q000031:analogs & derivatives* / Q000737:chemistry; D013696:Temperature
C051624:2-methylproline; D011392:Proline; D001920:Bradykinin