Equilibrium of conformers in solution: spin‐labelled angiotensin

Vesterman, B.; Sekacis, Ilmars; Betins, J.; Podiņš, L.; Nikiforovich, Gregory V.

doi:10.1016/0014-5793(85)80057-0

Cited by 4 publications

(3 citation statements)

References 2 publications

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“…Acetyl-TOAC-α-MSH and N-terminal TOAC derivatives of angiotensin , and bradykinin demonstrated the first syntheses of spin-labeled peptide hormones that maintained biological activity. Furthermore, a series of three, TOAC-labeled, neuropeptide Y analogues maintained their ability to bind the G-protein-coupled receptor Y, demonstrating the ability to obtain structural information upon binding of the NPY ligand to its receptor .…”

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confidence: 99%

Electron Paramagnetic Resonance Studies of Functionally Active, Nitroxide Spin-Labeled Peptide Analogues of the C-Terminus of a G-Protein α Subunit

Eps

Anderson²,

Kisselev

et al. 2010

Biochemistry

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The C-terminal tail of the transducin alpha subunit, Gtα(340–350), is known to bind and stabilize the active conformation of rhodopsin upon photoactivation (R*). Five spin-labeled analogs of Gtα(340–350) demonstrated native-like activity in their ability to bind and stabilize R*. The spin label 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid (TOAC) was employed at interior sites within the peptide, whereas a Proxyl (3-carboxyl-2,2,5,5-tetramethyl-pyrrolidinyloxy) spin label was employed at the amino terminus of the peptide. Upon binding to R*, the electron paramagnetic resonance spectrum of TOAC343-Gtα(340–350) revealed greater immobilization of the nitroxide when compared to that of the N-terminal modified Proxyl-Gtα(340–350) analog. A double-labeled Proxyl/TOAC348-Gtα(340–350) was examined by DEER spectroscopy to determine the distribution of distances between the two nitroxides in the peptides when in solution and when bound to R*. TOAC and Proxyl spin labels in this GPCR-G-protein α-peptide system provide unique biophysical probes that can be used to explore the structure and conformational changes at the rhodopsin-G-protein interface.

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confidence: 99%

Electron Paramagnetic Resonance Studies of Functionally Active, Nitroxide Spin-Labeled Peptide Analogues of the C-Terminus of a G-Protein α Subunit

Eps

Anderson²,

Kisselev

et al. 2010

Biochemistry

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“…The present investigation employed the same compound as in (5,6), namely the spin-labelled derivative of angiotensin (SL-AT, Figure 1). AT is a well-known oligopeptide with a variety of biological actions.…”

Section: Peptide Under Investigationmentioning

confidence: 99%

“…C(-r)=Ci-r)CJ-r) [5] where C 0 ('t) is the correlation function for the overall motion; for the isotropic case: [6] and CJ-r) is the correlation function for the internal motions having the form:…”

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confidence: 99%

The Space Structure of a Conformationally Labile Oligopeptide in Solution: Angiotensin

Vesterman

Betins

et al. 1987

Journal of Biomolecular Structure and Dynamics

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The paper describes a new approach to the problem of space structure description for conformationally labile molecules existing in solution as a set of different conformers in dynamic equilibrium. In such a case the "average" model derived exclusively from physico-chemical data represents a virtual structure devoid of physical sense. The proposed approach involves the selection of statistical weights wi for molecular conformers in solution by combined use of spectroscopic data and energy calculations (including the Monte-Carlo technique). Consequently, it appears possible to confine the entire region of all wi values only by those points (wi) that provide a reasonable agreement between the results of calculations and the experimental data. The approach was put to trial by using the linear octapeptide angiotensin, a well-known bioregulator with a wide spectrum of action. The 1H NMR and fluorescence spectroscopy were used as a source of experimental evidence concerning the space structure of the peptide in aqueous solution. The spin-lattice relaxation rates induced by the spin label allowed to estimate simultaneously several parameters characterizing the distance between the spin label and different functional groups in the angiotensin molecule. At least 5 types of angiotensin conformers were shown to be "indispensable" to achieve a good agreement between the results of energy calculations and 1H NMR spectroscopy data obtained in solution. The statistical weight estimates for angiotensin conformers permit to predict, with a high degree of accuracy, the value of singlet-singlet energy transfer between the Phe and Tyr aromatic chromophores of the molecule in aqueous solution. The proposed approach to the description of conformationally labile molecules can be actually regarded as stepwise refinement of statistical weight limits for sets of low-energy conformers in solution upon accumulation of new experimental evidence. The same appears to apply to conformationally labile molecules of non-peptide nature.

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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

et al. 2009

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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 TOAC1-AII and inactive TOAC3-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 TOAC3-AII because of the proximity between the nitroxide and Tyr4. CD spectra showed that although both AII and TOAC1-AII presented flexible conformations in water, TOAC3-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 TOAC1-AII, different conformations were acquired by TOAC3-AII. The membrane environment has been hypothesized to shift conformational equilibria so as to stabilize the receptor-bound conformation of ligands. The fact that TOAC3-AII is unable to acquire conformations similar to those of native AII and partially active TOAC1-AII is probably the explanation for its lack of biological activity.

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Equilibrium of conformers in solution: spin‐labelled angiotensin

Cited by 4 publications

References 2 publications

Electron Paramagnetic Resonance Studies of Functionally Active, Nitroxide Spin-Labeled Peptide Analogues of the C-Terminus of a G-Protein α Subunit

Electron Paramagnetic Resonance Studies of Functionally Active, Nitroxide Spin-Labeled Peptide Analogues of the C-Terminus of a G-Protein α Subunit

The Space Structure of a Conformationally Labile Oligopeptide in Solution: Angiotensin

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

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