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 nuclear magnetic resonance of the proline 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 histidine protons far removed from the bond has not been previously observed in model compounds or peptides. The peptides thyroliberin (TRH), [3-MeHis2]-TRH, and [3-MeHis6]-, [Sar1,Al8]-, and Nalpha-acetylangiotensin II were found to similarly isomerize 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 has previously been 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 five angiotensin peptides in rat uterine strips and of the three TRH peptides by radioimmunoassay of released thyrotropin.

NMR study of the possible interaction in solution of angiotensin II with a peptide encoded by angiotensin II complementary RNA.

“…For example, the signals downfield from 6 ppm in the spectrum of IIA are due to tyrosine, while the most downfield resonance in the spectrum of All is due to proton H-2 of histidine. As previously noted (12,13) Fig. 1 b-d.…”

Binding of Cu+ and Cu2+ with peptides: Peptides = oxytocin, Arg8‐vasopressin, bradykinin, angiotensin‐I, substance‐P, somatostatin, and neurotensin

“…It exhibits different conformational states such as α ‐helix, β ‐turn, γ‐turn, and random coil in aqueous solution and is pH dependent. Angiotensin‐I also shows pH‐dependent cis ↔ trans isomerization in His 6 ‐Pro 7 to effect its bioactivity . The interaction of different metal ions with AngI gained significant attention because the metal cations cease such isomerization.…”

Comparison of the solution structures of angiotensin I & II

“…Structure-activity relationships studies from several laboratories have revealed the topological contribution of the individual amino acid residues of the active AII molecule [3][4][5]. These studies have included theoretical [6,7] physicochemical [8,9], and spectroscopic investigation [10][11][12][13][14][15][16] and have led to several models for the AII structure in solution. However, a great variety of structural features such as a helix [8,17,18,] b pleated sheet, b and c turn [15,19], charge relay [20,21] and other structures [6,22] have been proposed.…”