Active site studies of neurohypophyseal hormones. Comparison of oxytocin and arginine vasopressin analogs containing 2-D-tyrosine

Hruby, Victor J.; Upson, Donald A.; Yamamoto, Diane M.; Smith, Clark W.; Walter, Roderich

doi:10.1021/ja00504a037

Cited by 34 publications

(9 citation statements)

References 9 publications

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“…With analogue I, the cis Mpa 1 ‐Ica 2 peptide bond results in the location of the Ica 2 side chain over the 20‐membered ring of the peptide. Such conformation is consistent with the ‘biological active’ model proposed for the native OT (70). Consequently, the surface accessible of Ica 2 is noticeably smaller than for the equivalent residues in the remaining analogues (Figure 10).…”

Section: Resultssupporting

confidence: 89%

Conformational Preferences of Proline Derivatives Incorporated into Vasopressin Analogues: NMR and Molecular Modelling Studies

Sikorska¹,

Sobolewski

Kwiatkowska

2012

Chem Biol Drug Des

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In this study, arginine vasopressin analogues modified with proline derivatives - indoline-2-carboxylic acid (Ica), (2S,4R)-4-(naphthalene-2-ylmethyl)pyrrolidine-2-carboxylic acid (Nmp), (2S,4S)-4-aminopyroglutamic acid (APy) and (2R,4S)-4-aminopyroglutamic acid, (Apy) - were examined using NMR spectroscopy and molecular modelling methods. The results have shown that Ica is involved in the formation of the cis peptide bond. Moreover, it reduces to a great extent the conformational flexibility of the peptide. In turn, incorporation of (2S,4R)-Nmp stabilizes the backbone conformation, which is heavily influenced by the pyrrolidine ring. However, the aromatic part of the Nmp side chain exhibits a high degree of conformational freedom. With analogues IV and V, introduction of the 4-aminopyroglumatic acid reduces locally conformational space of the peptides, but it also results in weaker interactions with the dodecylphosphocholine/sodium dodecyl sulphate micelle. Admittedly, both analogues are adsorbed on the micelle's surface but they do not penetrate into its core. With analogue V, the interactions between the peptide and the micelle seem to be so weak that conformational equilibrium is established between different bound states.

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Section: Resultssupporting

confidence: 89%

Conformational Preferences of Proline Derivatives Incorporated into Vasopressin Analogues: NMR and Molecular Modelling Studies

Sikorska¹,

Sobolewski

Kwiatkowska

2012

Chem Biol Drug Des

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“…It should be remembered that apart from the reduction of the trans vs cis ratio in the peptide bond, this results in a steric constraint, suppression of the proton-donating ability of the NH group capable of hydrogen bonding and enhanced basicity of the carbonyl group [5]. It was also shown that further change of the L/D configuration is likely to alter the orientation of the side chains of the residues at positions 2 and 3 [6]. An additional reason for studying these analogues was the finding that after the synthesis of [MePhe 2 ,D-MePhe 3 ]AVP on an automatic peptide synthesizer, two products were obtained, A and B, which had identical molecular ions and different retention times on HPLC ( Table 1).…”

Section: Introductionmentioning

confidence: 99%

Investigation of cis/trans ratios of peptide bonds in AVP analogues containing N‐methylphenylalanine enantiomers

Sikorska¹,

Ślusarz²,

Ślusarz³

et al. 2005

Journal of Peptide Science

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The solution conformation of vasopressin analogues, modified at positions 2 and 3 with N-methylphenylalanine or its enantiomer, [D-MePhe2,MePhe3]AVP and [MePhe2,D-MePhe3]AVP, were studied by 2D NMR spectroscopy in H2O/D2O and theoretical calculations (EDMC/ANALYZE). In the case of [MePhe2,D-MePhe3]AVP, the synthesis afforded two products, A and B, which had identical molecular ions and similar retention times on HPLC. This finding was explained by racemization of Cys1, which gave an additional analogue, [D-Cys1,MePhe2,D-MePhe3]AVP (B). The possibility is not excluded of racemization of Cys1 in the remaining analogues of this series. However, only in the case of [MePhe2,D-MePhe3]AVP was this process so distinct that two strong peaks in the HPLC chromatogram were observed. The NMR spectra of all the analogues showed several distinct sets of residual proton resonances. This suggests that the peptides adopt more than two groups of conformations in H2O/D2O. This fact is due to cis/trans isomerization. Two more populated isomers arise from the cis/trans isomerization across the 2-3 peptide bond in [D-MePhe2,MePhe3]AVP and [MePhe2,D-MePhe3]AVP (A) and across the 1-2 peptide bond in [D-Cys1,MePhe2,D-MePhe3]AVP (B).

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“…4. Assignments were made by comparison with known positions of resonances due to the component amino acids (10,11) and by comparison with the chemical shifts of the amino acid residues in other oligopeptides (1 [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18].…”

Section: Resultsmentioning

confidence: 99%

Conformational properties of the pentapeptide fragment [32–36] of the thymic hormone thymopoietin

Tourwé

Coen²,

Hallenga

et al. 1984

International Journal of Peptide and Protein Research

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The conformational energy for the pentapeptide Arg‐Lys‐Asp‐Val‐Tyr (TP5) is calculated using empirical potential functions. Calculation of the local interactions for each independent residue gives a local energy term for which the probabilities as a function of ø, ø are plotted on Ramachandran‐type maps. The interaction energy between residues is calculated only for these points in the maps with maximum probability. The most probable conformation for TP5 is found to have an extended backbone arrangement having the Arg and Tyr side‐chains folded over the backbone. 13C n.m.r. spin lattice relaxation time measurements show no increase in T1 of the α‐carbons at the first and terminal amino acids. The increase in T1 along the sidechain as found for Lys does not occur for Arg and Tyr. These signs of reduced mobility are consistent with a set of folded conformations in which the Arg and Tyr sidechains have hindered internal rotations. The vicinal NH‐CαH couplings agree well with those calculated for the most probable conformer. This is not so for the CαH‐CβH couplings. These data are consistent with previous n.m.r. and structure activity studies.

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Active site studies of neurohypophyseal hormones. Comparison of oxytocin and arginine vasopressin analogs containing 2-D-tyrosine

Cited by 34 publications

References 9 publications

Conformational Preferences of Proline Derivatives Incorporated into Vasopressin Analogues: NMR and Molecular Modelling Studies

Conformational Preferences of Proline Derivatives Incorporated into Vasopressin Analogues: NMR and Molecular Modelling Studies

Investigation of cis/trans ratios of peptide bonds in AVP analogues containing N‐methylphenylalanine enantiomers

Conformational properties of the pentapeptide fragment [32–36] of the thymic hormone thymopoietin

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