CD-n.m.r. study of the solution conformation of bradykinin analogs containing alpha-aminoisobutyric acid.
The conformation in aqueous solution of several alpha-aminoisobutyric acid (AIB)-containing analogs of bradykinin (BK) has been probed by complementary CD and 1H n.m.r. measurements. The conclusion reached is that substitution of AIB for Pro2 and/or Pro3 in BK stabilizes a degree of beta-turn conformation in the N-terminal tetrapeptide moiety of the resulting analogs. Changing the solvent from water to DMSO or TFE further enhances the contribution of particular hydrogen bonded structures to the time-averaged conformation of these peptides. Bradykinin and [AIB7]-BK adopt similar hydrogen bonded conformations in TFE, apparently with a contribution from a beta-turn involving their common Arg1-Pro2-Pro3-Gly4 moiety. The contrasting biological activities of BK and its AIB-analogs are considered in terms of the conformational analogy between the AIB-residue and cis' Pro and the propensity for a beta-turn at the N-terminus of the peptide.
D000595:Amino Acid Sequence; D000621:Aminoisobutyric Acids; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D002942:Circular Dichroism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D011487:Protein Conformation; D012996:Solutions; D013056:Spectrophotometry, Ultraviolet / Q000379:methods; D013329:Structure-Activity Relationship
D000621:Aminoisobutyric Acids; D012996:Solutions; C100049:2-aminoisobutyric acid; D001920:Bradykinin