Angiotensin II Conformations

Abstract

Vibrational spectra of angiotensinamide 11, some constitutive peptides, and an analog, are presented. Comparison of data for the solid hormone with those for the subunits yielded amide vibrations of the former in the 500-1700 cm-l range. Angiotensinamide I1 was shown to adopt a preferential antiparallel , ! ? conformation in both the solid state and concentrated aqueous solutions. Conformational information obtained by other methods are discussed together with the present results.The data pertinent to the behavior of hormone specific receptor sites [l] delineate with increasing accuracy their mechanical character. They require an agonist of very precise structure, which by being locked in the receptor frame may be submitted to structural changes and induce conformational variations. To define the structure of the hormone itself before and after such an event in the receptor is an exciting challenge and the more so when the hormone is a peptide. Therefore, a better knowledge of the conformational characteristics of a peptidic hormone placed in a variety of conditions seems to be a preliminary step towards the solution of the problem defined above.I n addition it is very likely that no additive energy besides that resulting from interactions with the receptor, the surrounding medium and within the molecule itself, is required to give the hormone its specific structure.On these bases we undertook study of angiotensin I1 conformations as this molecule seemed to afford an interesting example of the environmental influence. As a matter of fact, this octapeptide of linear primary structure appears to adopt in dilute aqueous solution two main conformations detectable by di- [S]. The required folding of the molecule was assigned principally to the hydrophobic interactions between the 3 and 5 valine and the 8 phenylalanine side-chains and to the cis conformation of the histidine-proline peptide bond. Interestingly enough, dry films of angiotensin I1 yielded circular dichroism spectra also reminiscent of a pleated sheet structure. We wished to check these conclusions with independent techniques in order to assess the validity of the approach used.The present paper is devoted to a study of angiotensin I1 in the solid state and concentrated aqueous solutions by infrared and Raman spectroscopy.Early infrared work had suggested empirical relations between the vibration bands of the peptide bonds and the structure of polypeptides [9,10]. The theory of Rliyazawa [ll, 121, despite some possible inadequacies [ 131, rationalized the amide bands conformation correlations for homopolypeptides [14], and also permitted fruitful investigations of protein

Comparison of the solution structures of angiotensin I & II

“…Finally, it should be noted that the structural feature of this NMR AII model exhibits great similarity with the model proposed by Fermandjian et al . [15] which exhibits one β‐turn at each terminus while Tyr4 and His6 rings are parallel and Phe8 ring is far apart [15].…”

Conformational Features of Bradykinin

“…For the interpretation of the CD results to be valid, this confirmation was necessary, but it could not be effected by NMR spectroscopy for lack of peptide material. With the exception of bands attributable to the phenylalanyl and TyrOMe sidechains (1513 cm-' [17], 1496 cm-', 1246 cm-', 745 cm-l and 702 cm-') no deviations in band position and relative intensity were observed. It appears thus that within the limitr of the method, conformational homogeneity of those peptides can be assumed.…”

Peptides as Therapeutic Agents or Drug Leads for Autoimmune, Hormone Dependent and Cardiovascular Diseases

“…al. (1972) proposed the antiparallel beta conformation model [108], and finally Moore and proposed the charge relay system and aromatic ring cluster between Tyr 4 -His 6 -Phe 8 [109].…”