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Conformational properties of angiotensin II and its active and inactive TOAC‐labeled analogs in the presence of micelles. Electron paramagnetic resonance, fluorescence, and circular dichroism studies
Author(s) -
Vieira Renata F. F.,
Casallanovo Fábio,
Marín Nélida,
Paiva Antonio C. M.,
Schreier Shirley,
Nakaie Clóvis R.
Publication year - 2009
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.21295
Subject(s) - chemistry , micelle , electron paramagnetic resonance , nitroxide mediated radical polymerization , circular dichroism , intramolecular force , crystallography , conformational change , spin label , stereochemistry , angiotensin ii , aqueous solution , nuclear magnetic resonance , organic chemistry , membrane , biochemistry , receptor , physics , copolymer , polymer , radical polymerization
The interaction between angiotensin II (AII, DRVYIHPF) and its analogs carrying 2,2,6,6‐tetramethylpiperidine‐1‐oxyl‐4‐amino‐4‐carboxylic acid (TOAC) and detergents —negatively charged sodium dodecyl sulfate (SDS) and zwitterionic N ‐hexadecyl‐ N,N ‐dimethyl‐3‐ammonio‐1‐propanesulfonate (HPS)—was examined by means of EPR, CD, and fluorescence. EPR spectra of partially active TOAC 1 ‐AII and inactive TOAC 3 ‐AII in aqueous solution indicated fast tumbling, the freedom of motion being greater at the N‐terminus. Line broadening occurred upon interaction with micelles. Below SDS critical micelle concentration, broader lines indicated complex formation with tighter molecular packing than in micelles. Small changes in hyperfine splittings evinced TOAC location at the micelle‐water interface. The interaction with anionic micelles was more effective than with zwitterionic micelles. Peptide‐micelle interaction caused fluorescence increase. The TOAC‐promoted intramolecular fluorescence quenching was more pronounced for TOAC 3 ‐AII because of the proximity between the nitroxide and Tyr 4 . CD spectra showed that although both AII and TOAC 1 ‐AII presented flexible conformations in water, TOAC 3 ‐AII displayed conformational restriction because of the TOAC‐imposed bend (Schreier et al., Biopolymers 2004, 74, 389). In HPS, conformational changes were observed for the labeled peptides at neutral and basic pH. In SDS, all peptides underwent pH‐dependent conformational changes. Although the spectra suggested similar folds for AII and TOAC 1 ‐AII, different conformations were acquired by TOAC 3 ‐AII. The membrane environment has been hypothesized to shift conformational equilibria so as to stabilize the receptor‐bound conformation of ligands. The fact that TOAC 3 ‐AII is unable to acquire conformations similar to those of native AII and partially active TOAC 1 ‐AII is probably the explanation for its lack of biological activity. © 2009 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 92: 525–537, 2009. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com