Conformations in solution of angiotensin II, and its 1–7 and 1–6 fragments

Cushman, J. A.; Mishra, Prasanna K.; Bothner‐By, Aksel A.; Khosla, Mala

doi:10.1002/bip.360320905

Cited by 14 publications

(9 citation statements)

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“…According to some authors (43)(44)(45)(46), the positions of the residues on the AII molecule determined the degree of pressor activity because of the stabilization of bioactive conformations anchoring, and interactions with the hormone receptor. Results obtained using techniques such as NMR, CD spectroscopy and Xray diffraction (47)(48)(49)(50)(51), in addition to theoretical calculations, suggest that the preferential compact folded structure is adopted. This is thought to be a result of the proximity of its amino and carboxy charged terminal extremities (51,52) and the interaction between the Tyr 4 and Phe 8 aromatic side chains (53,54), mediated by the presence of the His 6 side chain.…”

Section: Discussionmentioning

confidence: 99%

Highly Potential Antiplasmodial Restricted Peptides

et al. 2014

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Malaria is an infectious disease responsible for approximately one million deaths annually. The antimalarial effects of angiotensin II and its analogs against Plasmodium gallinaceum and P. falciparum have recently been reported. To evaluate antiplasmodial activity, we synthesized five angiotensin II-restricted analogs containing disulfide bridges. To accomplish this, peptides containing two inserted amino acid residues (cysteine) were synthesized by the Fmoc solid-phase method, purified by liquid chromatography, and characterized by mass spectrometry. Conformational studies were performed by circular dichroism. The results indicated that two of the analogs had higher antiplasmodium activity (92% and 98% activity) than angiotensin II (88% activity), measured by fluorescence microscopy. Results showed that the insertion position must be selected, to preserve the hydrophobic interactions between the non-polar residues, as this affects antiplasmodial activity. The circular dichroism studies suggested that the active analogs as well as the native angiotensin II adopt a β-turn conformation in different solutions. This approach provided insight for understanding the effects of restricting the ring size and position on the bioactivity of angiotensin II and provides a new direction for the design of potential chemotherapeutic agents.

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Section: Discussionmentioning

confidence: 99%

Highly Potential Antiplasmodial Restricted Peptides

et al. 2014

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“…1 Ang II is an octapeptide hormone (Asp1-Arg2-Val3-Tyr4-Ile5-His6-Pro7-Phe8, DRVYIHPF) that has been studied for several decades in the structure-dependent activity of the biological pathway of the Ang II receptor. [2][3][4][5][6][7][8][9][10][11][12][13] Free Ang II molecular structures in solutions have been investigated with a variety of techniques. The results have been reported as β-turn, random coil, hair-pin and other structures.…”

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confidence: 99%

“…The results have been reported as β-turn, random coil, hair-pin and other structures. [2][3][4][5][6][7][8] The structures of Ang II complexed with a receptor have been reported as a hair-pin or an extended structure in NMR and crystallography studies. [9][10][11][12][13] It is evident that several reports are not consistent with each other and that no clear agreement exists regarding the biologically active structure of Ang II during the biological process.…”

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confidence: 99%

Determination of a Binding Site of Cu, Ni, Mg, and Ca Metal Ions with Angiotensin II Peptide by Electrospray Tandem Mass Spectrometry

Kim¹,

Kim²,

Kim³

2010

Bulletin of the Korean Chemical Society

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Angiotensin II (Ang II) is the main active hormone in the renin-angiotensin blood pressure regulation system. 1 Ang II is an octapeptide hormone (Asp1-Arg2-Val3-Tyr4-Ile5-His6-Pro7-Phe8, DRVYIHPF) that has been studied for several decades in the structure-dependent activity of the biological pathway of the Ang II receptor. [2][3][4][5][6][7][8][9][10][11][12][13] Free Ang II molecular structures in solutions have been investigated with a variety of techniques. The results have been reported as β-turn, random coil, hair-pin and other structures.2-8 The structures of Ang II complexed with a receptor have been reported as a hair-pin or an extended structure in NMR and crystallography studies. [9][10][11][12][13] It is evident that several reports are not consistent with each other and that no clear agreement exists regarding the biologically active structure of Ang II during the biological process.For the study of blood pressure control and metal-peptide interaction, the influences of metal cations on the biological activity of Ang II have been also investigated. , and Ca 2+ ) and the Ang II molecule to explain the biological effect in terms of a gas-phase structural difference. We present the results of a tandem mass spectrometry and multiple mass spectrometry study regarding the interaction of metal ions with the Ang II molecule, the C-terminus amidated Ang II molecule (DRVYIHPF-NH 2 ), and two of its segments: the N-terminus tetrapeptide Asp1-Arg2-Val3-Tyr4-NH2 (DRVY-NH2) and the N-terminus hexapeptide Asp1-Arg2-Val3-Tyr4-Ile5-His6-NH2 (DRVYIH-NH2). Two N-terminus segments are used to confirm the [metal II + Ang II] 2+ complex formation efficiency and the metal binding site. Experimental SectionThe gas-phase [metal II + Ang II] 2+ cation complexes were produced by an electrospray ionization source. The experimental MS/MS and MS/MS/MS spectra for fragmentation pattern analysis were obtained using a Thermo Finnigan LTQ mass spectrometer (Thermo Electron Corp., San Jose, CA, USA). This mass spectrometer is a linear ion trap mass spectrometer equipped with an atmospheric pressure-ionization source. LTQ conditions. The samples were introduced into the electrospray interface by a direct infusion method using a microsyringe pump (SGE, Australia) at a flow rate of 5 µL min. The MS/MS spectra were acquired with experimental conditions of an isolation width of 0.5 -1 mass unit, an activation time of 30 msec and q z = 0.25. In MS/MS or MS/MS/MS mode, the parent ion molecules were manually selected one by one, and each was subjected to collision-induced dissociation (CID).Reagents. Ang II human (96%, Fluka), DRVYIHPF-NH2 (> 90%, Peptron, Daejeon, Korea), DRVY-NH2 (> 90%, Peptron, Daejeon, Korea), DRVYIH-NH2 (> 90%, Peptron, Daejeon, Korea), CuCl 2 ․2H 2 O (99%, Sigma-Aldrich Korea), Ni(NO 5 ) 2 ․ 6H2O (97%, Junsei chemical Co., Tokyo, Japan), CaCl2․2H2O (98%, Daejung Chemical Korea), Mg(NO3)2․6H2O (98%, Junsei chemical Co., Tokyo, Japan), and H2O (HPLC grade, Merck) were used in experiments. Ang II was dissolved in water to...

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“…AII has been extensively investigated in solution during the last 40 years with a variety of techniques, including theoretical, physicochemical, and spectroscopic. The results have been interpreted in terms of various models such as an a-helix [13], b-turn [14][15][16][17], cross-b-forms II [18], antiparallel pleated sheet [19,20], c-turn [19], random coil [21,22], inverse c-turn [23], side chain ring cluster [24], and other structures [25][26][27][28][29]. It is evident that several of the reported models are not consistent with each other and that there is no general consensus on the solution conformation of AII.…”

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On the molecular basis of the recognition of angiotensin II (AII)

Tzakos

Bonvin²,

Troganis

et al. 2003

European Journal of Biochemistry

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The high-resolution 3D structure of the octapeptide hormone angiotensin II (AII) in aqueous solution has been obtained by simulated annealing calculations, using highresolution NMR-derived restraints. After final refinement in explicit water, a family of 13 structures was obtained with a backbone RMSD of 0.73 ± 0.23 Å . AII adopts a fairly compact folded structure, with its C-terminus and N-terminus approaching to within 7.2 Å of each other. The side chains of Arg2, Tyr4, Ile5 and His6 are oriented on one side of a plane defined by the peptide backbone, and the Val3 and Pro7 are pointing in opposite directions. The stabilization of the folded conformation can be explained by the stacking of the Val3 side chain with the Pro7 ring and by a hydrophobic cluster formed by the Tyr4, Ile5 and His6 side chains. Comparison between the NMR-derived structure of AII in aqueous solution and the refined crystal structure of the complex of AII with a high-affinity mAb (Fab131) [Garcia, K.C., Ronco, P.M., Verroust, P.J., Brunger, A.T., Amzel, L.M. (1992) Science 257, 502-507] provides important quantitative information on two common structural features: (a) a U-shaped structure of the Tyr4-Ile5-His6-Pro7 sequence, which is the most immunogenic epitope of the peptide, with the Asp1 side chain oriented towards the interior of the turn approaching the C-terminus; (b) an Asxturn-like motif with the side chain aspartate carboxyl group hydrogen-bonded to the main chain NH group of Arg2. It can be concluded that small rearrangements of the epitope 4-7 in the solution structure of AII are required by a mean value of 0.76 ± 0.03 Å for structure alignment and 1.27 ± 0.02 Å for sequence alignment with the X-ray structure of AII bound to the mAb Fab131. These data are interpreted in terms of a biological ÔnucleusÕ conformation of the hormone in solution, which requires a limited number of structural rearrangements for receptor-antigen recognition and binding.Keywords: angiotensin II; monoclonal antibody; NMR; peptide structure; VIb turn.Angiotensin II (AII), the main effector octapeptide hormone (Asp1-Arg2-Val3-Tyr4-Ile5-His6-Pro7-Phe8) of the renin-angiotesin system [1], exerts a variety of actions on different target organs via specific receptors designated AT 1 and AT 2 [2,3]. Most of the known physiological effects of AII have been attributed to AT 1 , e.g. vasoconstriction, aldosterone release, renal sodium reabsorption, as well as central osmoregulatory actions, including the release of pituitary hormones into the circulation and growth stimulation in various cell types. These effects constitute the role of angiotensin peptides as neuromodulators/neurotransmitters in the brain. Because of the variety of biological and physiological actions of AII in various tissues, intensive research is required to determine the structural features of this phylogenetic hormone. This should provide the structural basis for the biological pathway of conformationinformation-transformation.For peptide ligand-receptor interactions, there are three genera...

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Conformations in solution of angiotensin II, and its 1–7 and 1–6 fragments

Cited by 14 publications

References 40 publications

Highly Potential Antiplasmodial Restricted Peptides

Highly Potential Antiplasmodial Restricted Peptides

Determination of a Binding Site of Cu, Ni, Mg, and Ca Metal Ions with Angiotensin II Peptide by Electrospray Tandem Mass Spectrometry

On the molecular basis of the recognition of angiotensin II (AII)

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