Antagonists of substance P. Further modifications of SP antagonists obtained by replacing either positions 7, 9 or 7, 8 and 11 of SP with D-amino acid residues

Dutta, Anand S.; Gormley, James J.; Graham, Anthony S.; Briggs, Ian; Growcott, Jim; Jamieson, Alec

doi:10.1021/jm00157a009

Cited by 10 publications

(1 citation statement)

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“…One flCH2S] hexapeptide has been shown earlier (19) to antagonize substance P and substance P(6-11) on the guinea-pig ileum. However, since the corresponding all-amide peptide was not available, and since no degradation pattern was reported, the contribution of the pseudopeptide link to the activity increase could not be ' assessed.…”

Section: Biological Activitymentioning

confidence: 98%

Synthesis and in vitro activities of new tryptophan-modified and thiomethylene-containing pseudopeptide antagonists of the neurokinins

Paladino

Thurieau

Morris

et al. 2009

International Journal of Peptide and Protein Research

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A series of pseudopeptide analogs of the substance P-like hexapeptide Ava-Phe-Phe-Gly-Leu-Met-NH2 was produced by N,-protection, introduction of the thiomethylene bond, of D-and non-proteinogenic amino acids, and alteration of the side chain of tryptophan. Synthesis of the pseudopeptides on a solid phase was successfully improved by direct formation of the CH2-S bond on the resin. However, while thiomethylene formation between leucine and norleucine led to the expected SS diastereoisomer, the major product of the similar coupling between two phenylalanines was the SR isomer. An improved resistance of the analogs to proteolysis was observed, which could be related to the structural changes. Interestingly, these modifications led to three water-soluble and potent neurokinin antagonists on classical in vitro bioassays. 0 Munksgaard 1993.

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Section: Biological Activitymentioning

confidence: 98%

Synthesis and in vitro activities of new tryptophan-modified and thiomethylene-containing pseudopeptide antagonists of the neurokinins

Paladino

Thurieau

Morris

et al. 2009

International Journal of Peptide and Protein Research

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Molecular dynamics simulation provides a possible structure for substance P‐like peptides in aqueous solution

Teleman¹,

Lieth²

1990

Biopolymers

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A hypothetical conformation of the undecapeptide Substance P in aqueous solution is generated by molecular dynamics simulation for 284 ps. The conformation takes explicit solvent interactions into account as well as entropic effects to the extent that phase space is sampled in simulation. The initial conformation is taken from energy minimization studies and modified. In spite of fluctuations through 180 degrees in some backbone dihedral angles, the peptide settles with all backbone dihedrals within +/- 60 degrees from the initial values. In 130 ps, the radius of gyration decreases from 6.2 A to 5.5 A, whereas only fluctuation (+/- .2 A) is observed during the last 150 ps. The root-mean-square deviation at optimal superposition for a pair of conformations from the last 150 ps is 0.6 A, based on backbone atoms. The final structure is close-knit, nearly globular, and stabilized by several long-lived hydrogen bonds. The simulation conformation agrees with the scarce experimental data including a large number of structure-activity relationships. Thus, the simulation conformation is a likely candidate for one of the several conformations, the existence of which has been deduced from nuclear magnetic resonance data. Simulation results and experimental modification studies suggest that Phe 8 and Leu 10 are involved in the primary binding of SP to its receptors.

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ChemInform Abstract: Antagonists of Substance P. Further Modifications of Substance P Antagonists Obtained by Replacing either Positions 7, 9 or 7, 8 and 11 of SP with D‐Amino Acid Residues.

Dutta¹,

Gormley²,

Graham³

et al. 1986

Chemischer Informationsdienst

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Antagonists of substance P. Further modifications of SP antagonists obtained by replacing either positions 7, 9 or 7, 8 and 11 of SP with D-amino acid residues

Cited by 10 publications

References 0 publications

Synthesis and in vitro activities of new tryptophan-modified and thiomethylene-containing pseudopeptide antagonists of the neurokinins

Synthesis and in vitro activities of new tryptophan-modified and thiomethylene-containing pseudopeptide antagonists of the neurokinins

Molecular dynamics simulation provides a possible structure for substance P‐like peptides in aqueous solution

ChemInform Abstract: Antagonists of Substance P. Further Modifications of Substance P Antagonists Obtained by Replacing either Positions 7, 9 or 7, 8 and 11 of SP with D‐Amino Acid Residues.

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