Circular-Dichroism Spectra of Truncated and Other Analogs of Angiotensin II

Abstract

Circular dichroism spectra on angiotensin I1 and analogs, and its truncated N-terminal and C-terminal peptides were determined in fluorinated alcohols under several conditions in the peptide or aromatic spectral regions. The following conclusions were suggested : (a) evidence for a structure for angiotensin 11; (b) evidence for a folding at the N-terminal and C-terminal part of the molecule; (c) an interaction involving the C-terminal residue which decreases progressively when phenylalanine is replaced by isoleucine and then by alanine; (d) the N-terminal amino acid seems to play an important role in the overall conformation of the molecule possibly by interacting with the C-terminus, its absence in the 2-8 heptapeptide giving rise to a more pronounced signal than angiotensin 11; (e) in trifluoroethanol the conformation of these peptides is well defined and fits well with observed structure-activity relationships and observed binding data. There is a loss of this relationship when these solvents are diluted with water.Previous studies on angiotensin 11, Asp-Arg-ValTyr-Ile/Val-His-Pro-Phe, have yielded several suggested conformations including an anti-parallel fi conformation for this peptide, especially in non-polar solvents. Also, previous structure-activity studies of octapeptide analogs of angiotensin I1 have determined the side groups important for biological activity [l -31. However, structure activity data cannot distinguish between side groups involved in peptide-receptor interactions and side groups involved in providing conformational stability to the peptide. To further examine the conformation of the peptide, we have used the technique of circular dichroism (CD) which gives general information about the overall conformation of peptides and proteins. However, the interpretation of data is still difficult for the former compounds. To improve our interpretation of CD spectra for angiotensin-related peptides and to attempt to relate primary structure to conformation to biological activity, we have prepared a series of truncated angiotensionll analogs in which amino acid residues have been eliminated one at a time from either the N-terminus or the C-terminus. These truncated sequences and a few selected octapeptide analogs have been examined in fluorinated alcohols because (a) the peptides have a well-defined conformation in these solvent systems Abbreriations. CD, circular dichroism ; NMR, nuclear magnetic resonance; F,EtOH, trifluoroethanol ; F,iPrOH, hexdfluoroisopropanol; Boc, t-butyloxycarbonyl.[4], which is not true in aqueous solution, and (b) previous studies have indicated that there is a good relationship between the assigned conformation in these solvents and binding characteristics of these peptides to the isolated membranes and 'solubilized receptors' [5 -71. EXPERIMENTAL PROCEDURE Meusurement of CD SpectraThe circular dichroism spectra were determined on a Roussel Jouan 185, model1 I1 Diochograph. Absorption spectra were recorded using a Jouan Spectral DF 170 spectrophotometer. Peptide concen...

Conformational Features of Bradykinin

“…Whereas the pH dependence of the difference spectra is well correlated between the ' L b and 'Lo, ' B bands in these peptides, it is surprising that the rather remarkable solvent effect of FsEtOH in the near-ultraviolet CD spectra is so weakly evident in the peptide region, especially with respect to residue 8. In this context we are reminded of the fact that the solvent effect H,0/F3EtOH for the entire far-ultraviolet CD spectrum of bradykinin, as shown by Marlborough et al [9] and confirmed by our studies, is rather small in comparison to what has been observed in the case of angiotensin 11 [26] and adrenocorticotropin [27]. Evidently the three transitions 'Lb, ' L , and ' B are not affected equally every time an outer parameter changes in any way.…”

Mycobacterium tuberculosisChaperonin 10 Is Secreted in the Macrophage Phagosome: Is Secretion Due to Dissociation and Adoption of a Partially Helical Structure at the Membrane?

“…Although it could be argued that the structural transition to ␣-helix seen here may be due to the ␣-helical stabilizing effects of organic solvents such as TFE (33), there are a number of observations that support the conclusion of a genuine propensity for the M. tuberculosis Cpn10 monomer to form partially helical structures. Firstly, regions without helical propensity do not form helices even in 100% TFE (26,43), and other structures (e.g., ␤-turn and ␤-sheet) are supported by this solvent (14,15,42). Secondly, a partially helical monomer exists also in the absence of organic solvents, albeit at a very low concentration (Fossati et al, submitted).…”

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