Conformational analysis of [Cpp1, Sar7, Arg8] vasopressin by 1H‐NMR spectroscopy and molecular mechanics calculations

Shenderovich, Mark D.; Kasprzykowski, Franciszek; Liwo, Adam; Sekacis, Ilmars; Saulitis, Juris; Nikiforovich, Gregory V.

doi:10.1111/j.1399-3011.1991.tb01536.x

Cited by 14 publications

(1 citation statement)

References 31 publications

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“…Similarly, the theoretical investigations of AVP structures in vacuum propose the appearance of β ‐turn at positions 3,4 and 4,5 (9). Furthermore, the main structural elements of bioactive analogues of AVP are reverse structures in cyclic part of peptides (10–12). The possibility of formation of β ‐turns in cyclic part of molecules increases with incorporation in positions 2 or 3, the amino acid with D configuration (13).…”

Section: Introductionmentioning

confidence: 99%

Conformational studies of highly potent 1‐aminocyclohexane‐1‐carboxylic acid substituted V₂ vasopressin agonists

Sikorska

Ślusarz

Lammek

2005

The Journal of Peptide Research

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Conformational studies of three agonists of V2 receptor modified with 1‐aminocyclohexane‐1‐carboxylic acid (Acc), [Acc2,DArg8]VP, [Acc3]AVP and [Cpa1,Acc3]AVP, using 2D NMR and theoretical calculations are presented in this paper. It is believed that α,α‐disubstituted amino acids, such as Acc, affect the formation of either 310 or α‐helical conformation. Moreover, a peptide with Acc may adopt either the γ‐ or an inverse γ‐turn over it. Thus, incorporation of Acc into the arginine‐vasopressin sequence induced C7‐membered ring conformation with Acc at the top of it, and additional formation of β‐bend involving residues in the 2–5 fragment of the peptides. Furthermore, the analogues are also characterized by type I of β‐turn involving residues Acc3‐Cys6 in [Acc3]AVP and [Cpa1,Acc3]AVP, and by type IV or II′ in [Acc2,DArg8]VP. Replacement of Tyr at position 2 of [Acc2,DArg8]VP with Acc afforded a hydrogen bond between the guanidine moiety of DArg8 and the side chain of either Asn5 or Gln4. In the remaining analogues, the β‐turn comprising the Cys6‐Gly9 residues allows the positively charged side chain of Arg8 to be directed toward Tyr2. The substitution of Cys1 with Cpa1 enhances hydrophobic properties of N‐terminal part of the molecule strengthening thereby the affinity to the binding pocket of receptors.

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Section: Introductionmentioning

confidence: 99%

Conformational studies of highly potent 1‐aminocyclohexane‐1‐carboxylic acid substituted V₂ vasopressin agonists

Sikorska

Ślusarz

Lammek

2005

The Journal of Peptide Research

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Exploration of the conformational space of oxytocin and arginine-vasopressin using the electrostatically driven Monte Carlo and molecular dynamics methods

et al. 1998

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Conformational analysis of the neurohypophyseal hormones oxytocin (OT) and arginine‐vasopressin (AVP) has been carried out using two different computational approaches and three force fields, namely by the Electrostatically Driven Monte Carlo (EDMC) method, with the Empirical Conformational Energy Program for Peptides (ECEPP/3) force field or with the ECEPP/3 force field plus a hydration‐shell model, and by simulated‐annealing molecular dynamics with the Consistent Valence Force Field (CVFF). The low‐energy conformations obtained for both hormones were classified using the minimal‐tree clustering algorithm and characterized according to the locations of β‐turns in the cyclic moieties. Calculations with the CVFF force field located conformations with a β‐turn at residues 3 and 4 as the lowest energy ones both for OT and for AVP. In the ECEPP/3 force field the lowest energy conformation of OT contained a β‐turn at residues 2 and 3, conformations with this location of the turn being higher in energy for AVP. The later difference can be attributed to the difference in the size of the side chain in position 3 of the sequences: the bulkier phenylalanine residue of AVP in combination with the bulky Tyr2 residue hinders the formation of a turn at residues 2 and 3. Conformations of OT and AVP with a turn at residues 3,4 were in the best agreement with the x‐ray structures of deaminooxytocin and pressinoic acid (the cyclic moiety of vasopressin), respectively, and with the nmr‐derived distance constraints. Generally, the low‐energy conformations obtained with the hydration‐shell model were in a better agreement with the experimental data than the conformations calculated in vacuo. It was found, however, that the obtained low‐energy conformations do not satisfy all of the nmr‐derived distance constraints and the nuclear Overhauser effect pattern observed in nmr studies can be fully explained only by assuming a dynamic equilibrium between conformations with β‐turns at residues 2.3, 3.4, and 4.5. The low‐energy structures of OT with a β‐turn at residues 2.3 have the disulfide ring conformations close to the model proposed recently for a potent bicyclic antagonist of OT [M.D. Shenderovich et al. (1994) Polish Journal of Chemistry, Vol. 25, pp. 921–927], although the native hormone differs from the bicyclic analogue by the conformation of the C‐terminal tripeptide. This finding confirms the hypothesis of different receptor‐bound conformations of agonists and antagonists of OT. © 1996 John Wiley & Sons, Inc.

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Conformational solution studies of [Sar⁷]desamino‐ and [MeAla⁷]desamino‐ vasopressin analogues using NMR spectroscopy

Rodziewicz‐Motowidło

Zhukov

Kasprzykowski

et al. 2002

Journal of Peptide Science

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Solution structures of two analogues of vasopressin with an amino acid sequence of c[Mpa1-Tyr2-Phe3-Gln4-Asn5-Cys6]-Xaa7-Arg8-Gly9-NH2 (Xaa = Sar [I] or MeAla [II]) were established using ROE and the 3J(HNH alpha) couplings. Each of the peptides was found to exist in two stable isomers, pertaining to the cis or trans status of the Cys6-Xaa7 peptide bond, thus giving rise to four study objects. Two methods for studies of the conformational properties of the structures were compared. In the first, the algorithm consisted of three steps: (i) An Electrostatically Driven Monte-Carlo (EDMC) search for low-energy conformations. (ii) Simulations of the NOESY spectra and the vicinal couplings for these conformations. (iii) Determination of the statistical weights of the conformations with the ANALYZE package, so as to meet the best fit of the averaged NOE intensities and couplings to the experimental data. In the second method, the distance constraints and the torsion angles were used as the usual constraints in the Distance Geometry and Simulated Annealing algorithms. The flexibility of the pressin ring and the C-terminus was characterized by a large number of families of conformations. The presence of the beta-turn at position 4,5 was confirmed for all low energy structures found. The use of the EDMC method for the elaboration of the NMR data for small flexible peptides yielded an adequate description of their conformational diversity and is the method of choice for the analysis of their solution structures.

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Conformational analysis of [Cpp¹, Sar⁷, Arg⁸] vasopressin by ¹H‐NMR spectroscopy and molecular mechanics calculations

Cited by 14 publications

References 31 publications

Conformational studies of highly potent 1‐aminocyclohexane‐1‐carboxylic acid substituted V₂ vasopressin agonists

Conformational studies of highly potent 1‐aminocyclohexane‐1‐carboxylic acid substituted V₂ vasopressin agonists

Exploration of the conformational space of oxytocin and arginine-vasopressin using the electrostatically driven Monte Carlo and molecular dynamics methods

Conformational solution studies of [Sar⁷]desamino‐ and [MeAla⁷]desamino‐ vasopressin analogues using NMR spectroscopy

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Conformational analysis of [Cpp1, Sar7, Arg8] vasopressin by 1H‐NMR spectroscopy and molecular mechanics calculations

Cited by 14 publications

References 31 publications

Conformational studies of highly potent 1‐aminocyclohexane‐1‐carboxylic acid substituted V2 vasopressin agonists

Conformational studies of highly potent 1‐aminocyclohexane‐1‐carboxylic acid substituted V2 vasopressin agonists

Exploration of the conformational space of oxytocin and arginine-vasopressin using the electrostatically driven Monte Carlo and molecular dynamics methods

Conformational solution studies of [Sar7]desamino‐ and [MeAla7]desamino‐ vasopressin analogues using NMR spectroscopy

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Conformational analysis of [Cpp¹, Sar⁷, Arg⁸] vasopressin by ¹H‐NMR spectroscopy and molecular mechanics calculations

Conformational studies of highly potent 1‐aminocyclohexane‐1‐carboxylic acid substituted V₂ vasopressin agonists

Conformational studies of highly potent 1‐aminocyclohexane‐1‐carboxylic acid substituted V₂ vasopressin agonists

Conformational solution studies of [Sar⁷]desamino‐ and [MeAla⁷]desamino‐ vasopressin analogues using NMR spectroscopy