Proposed Models for Angiotensin II in Aqueous Solution and Conclusions about Receptor Topography

Printz, Morton P.; Némethy, George; Bleich, Hermann E.

doi:10.1038/newbio237135a0

Cited by 77 publications

(61 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In trifluoroethanol, this peptide has two bends or turns; one located near the N-terminus and the second located near the C-terminus. Some proton NMR results support these facts even though the authors are not in full agreement on the type of bends occurring in the molecule of angiotensin I1 [17,25,26]. However, these studies were conducted in different conditions of solvent and temperature and we know, from our earlier work and from this study, that the conformation of angiotensin I1 is strongly dependent upon the microenvironment.…”

Section: Discussionsupporting

confidence: 56%

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

Greff¹,

Fermandjian²,

Fromageot³

et al. 1976

Eur J Biochem

View full text Add to dashboard Cite

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...

show abstract

Section: Discussionsupporting

confidence: 56%

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

Greff¹,

Fermandjian²,

Fromageot³

et al. 1976

Eur J Biochem

View full text Add to dashboard Cite

show abstract

“…For this reason, conformational studies on ANG II have been performed by many scientists using spectroscopic and X-ray crystallographic techniques [30][31][32][33][34][35][36][37]. We have developed a model supported by NMR (2D ROESY), fluorescence lifetime and molecular modeling studies [36,37].…”

Section: Resultsmentioning

confidence: 99%

Superimposition of potent non-peptide AT1 receptor antagonists with angiotensin II

et al. 1996

View full text Add to dashboard Cite

The model of angiotensin II (ANG II) developed in our laboratory using a combination of NMR, fluorescence data and molecular graphics [Matsoukas, J.M. et al., J. Biol. Chem., 269 (1994) 5303] served as a template for a systematic superimposition of potent AT~ receptor antagonists with ANG II. The key amino acids in this model, tyrosine, phenylalanine and histidine, form a charge-relay system. The studied ANG II AT~ receptor antagonists were found to accommodate this relay system. The proposed model offers a motivation to synthetic chemists to develop ANG II antagonists that differ from the losartan prototype structure but possess an enhanced biological profile.

show abstract

“…The y turn was first suggested by Printz and coworkers [25,26] as a stable conformational feature in connection with angiotensin I1 models and, as mentioned above, was also found to be expected on the basis of theoretical calculations [5] on the tripeptides Gly-Gly-Gly and Ala-Ala-Ala. The presence of the y tuin in solutions of elastin repeat peptides-the pentapeptide (VPGVG) and the hexapeptide (APGVGV) and their high polymers-has been proposed by this laboratory [l-3,27,28].…”

Section: Introductionmentioning

confidence: 90%

Nuclear magnetic resonance and conformational energy calculations of repeat peptides of tropoelastin: Correlation of 1J(15N-1H) with nonplanarity of peptide moiety

Renugopalakrishnan

Khaled

Okamoto

et al. 2009

Int. J. Quantum Chem.

View full text Add to dashboard Cite

Conformational energy calculations and 'H and I3C nuclear magnetic resonance ( N M R ) studies in CDCI3 of a tripeptide. N-Ac-Glyl-L-Val2-Cly~-OMe. suggested the Occurrence of an I I -membered hydrogen-bonded ring, or y-turn conformation. The theoretical calculations indicated that the Conformation occurs when there is a distortion of the planarity of the peptide moiety. An I5N N M R study of thc tripeptide in CDCI3 was undertaken to see if these spectral parameters might correlate with deviations from planarity. 'H, I3C, and 15N N M R studies were also carried out on the dipcptide N-hc-~.-Vall-Glyz-OMe, which argue for the occurrence of an 8-membered hydrogen-bonded ring. or CX conformation and even greater distortions from peptide planarity. Therefore a theoretical investigation of this problem, using both the empirical and molecular orbital calculations in the C N 1 ) 0 / 2 approximation, was undertaken, the results of which indicate large distortions of the planarity of the peptide moiety. While further work is required before the detailed functional depcndence of N M R parameters to planarity of the peptide moiety can be established, a systematic variation of the 'J(I5N-'H) coupling constant with peptide planarity is observed for the molecules discussed.

show abstract

Proposed Models for Angiotensin II in Aqueous Solution and Conclusions about Receptor Topography

Cited by 77 publications

References 20 publications

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

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

Superimposition of potent non-peptide AT1 receptor antagonists with angiotensin II

Nuclear magnetic resonance and conformational energy calculations of repeat peptides of tropoelastin: Correlation of 1J(15N-1H) with nonplanarity of peptide moiety

Contact Info

Product

Resources

About