s-Cis and s-trans isomerism of the His-Pro peptide bond in angiotensin and Thyroliberin analogs

Abstract

The dipeptide His-Pro isomerizes from all-s-trans to partly s-cis when titrated in D2O from acidic to neutral pD as observed by 13C and 1H NMR of the Pro side chain. This isomerization is reported by the His C-2 and C-4 protons and carbons which show distinct, well-resolved resonances for each isomer. The influence of the His-Pro peptide bond rotational state on the His protons far removed from the bond was not previously observed in model compounds or peptides. The peptides thyroliberin (TRH), [3-MeHis2]-TRH, and [3-MeHis6]-, [Sar1,Ala8]-, and N.alpha.-acetylangiotensin II similarly isomerized from all-s-trans to partly s-cis as reported by their His C-2 and C-4 proton resonances. The His C-2 and C-4 protons in the peptides [1,3-diMeHis2]-TRH and [1-MeHis6]-, and [homoHis6]-angiotensin do not report this isomerization. Angiotensin II was previously found to exhibit the same isomerization. The reporting of the s-trans to s-cis isomerization by the His C-2 proton appears to be correlated with the known potencies of the 5 angiotensin peptides in rat uterine strips and of the 3 TRH peptides by radioimmunoassay of released thyrotropin.