Probing the bradykinin receptor: mapping the geometric topography using ethers of hydroxyproline in novel peptides

Kyle, Donald J.; Martin, Jennifer A.; Burch, Ronald M.; Carter, John; Lu, Songfeng; Meeker, Sonya; Prosser, Judith C.; Sullivan, James P.; Togo, J

doi:10.1021/jm00112a047

Cited by 83 publications

(32 citation statements)

References 17 publications

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“…Therefore, BK receptor antagonists have been considered as constituting a potential drug for the management of such diseases. In the last two decades, a great number of peptide BK B 2 antagonists have been synthesised (Cheronis et al 1992;Kyle 1995;Kyle et al 1991;Lembeck et al 1991;Stewart 1995;Wirth et al 1991Wirth et al , 1994 and several pre-clinical pharmacological studies have shown that some of the peptide BK B 2 receptor antagonists have antiinflammatory and anti-hyperalgesic properties, suggesting their potential clinical use (Campos and Calixto 1995;283 Fig. 6 Effect of intraperitoneal (A) or oral (B) injection of NPC 18884 or intraperitoneal treatment with HOE 140 (Icatibant; C) on the bradykinin-induced licking in mice.…”

Section: Discussionmentioning

confidence: 99%

Oral antinociception and oedema inhibition produced by NPC 18884, a non-peptidic bradykinin B2 receptor antagonist

Campos

Alves

Ferreira

et al. 1999

Naunyn-Schmiedeberg's Arch Pharmacol

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This study investigates the antinociceptive and the oedema inhibition properties of the novel non-peptide bradykinin (BK) B2 receptor antagonist, NPC 18884. Given by i.p. or p.o. routes NPC 18884 produced graded and long-lasting (at least 2.5h and 5.0h, respectively, for i.p. and p.o. administration) inhibition of acetic acid-induced abdominal constrictions in mice, with mean ID50 values of 8.3 nmol/kg and 439.9 nmol/kg. NPC 18884 also inhibited kaolin-induced abdominal constrictions (44+/-9% and 48+/-3% of inhibition, for i.p. and p.o. routes, respectively). Given by i.p. or p.o. routes NPC 18884 attenuated both phases of formalin-induced licking, as well as formalin-induced oedema formation. At similar doses NPC 18884 produced significant inhibition of capsaicin-induced nociception. NPC 18884, like HOE 140 given i.p., prevented the nociception caused by BK with mean ID50 values of 0.85 nmol/kg and 0.44 nmol/kg, respectively. Given orally NPC 18884, but not HOE 140, caused graded inhibition of BK-induced nociception (mean ID50 value of 50 nmol/kg). In rats, NPC 18884 given i.p. prevented BK and carrageenan-induced hyperalgesia (mean ID50 values of 6 nmol/kg and 13 nmol/kg), without affecting the hyperalgesia induced by des-Arg9-bradykinin (DABK) or by prostaglandin E2 (PGE2). NPC 18884 given i.p. inhibited the mouse paw oedema induced by tyrosine8-bradykinin or by carrageenan, but had no effect on DABK-induced oedema in mice pre-treated with Escherichia coli endotoxin, or that induced by PGE2. Thus, the novel non-peptide BK B2 receptor antagonist NPC 18884 produces rapid onset, potent and relatively long-lasting oral antinociceptive and oedema inhibition properties. The anti-BK actions of NPC 18884 are quite selective towards the BK B2 receptor-mediated responses.

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Section: Discussionmentioning

confidence: 99%

Oral antinociception and oedema inhibition produced by NPC 18884, a non-peptidic bradykinin B2 receptor antagonist

Campos

Alves

Ferreira

et al. 1999

Naunyn-Schmiedeberg's Arch Pharmacol

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“…Moreover, compounds contained in this series represent the first examples of highly potent peptides (at least as potent as the DTic 7 -containing peptides) that do not contain an aromatic amino acid at position 7 as had been previously considered essential. The desired t3-tum was confirmed when the residue in position 7 was an alkyl ether of D-4-hydroxyproline in either the cis or trans geometric state and the eighth residue was Tic or Oic (99) .…”

Section: Structure Of the Bradykinin Binding Domain Of The B2 Receptormentioning

confidence: 90%

“…This, coupled to current developments in the understanding of the conformational structures of BK and its potent antagonists, while bound to the receptors (99,100,164) , may lead to a potent, selective nonpeptide antagonist of BK receptor sUbtypes. Such agents will be invaluable instruments for dissecting the intricacies of kinin receptor pharmacology, and may fu rther our knowl edge of the role of kinins in disease.…”

Section: Discussionmentioning

confidence: 99%

“…Recently reported are novel peptide Bz receptor antagonists that are not analogues of NPC 361, but rather are BK analogues containing modified amino acids in positions 7 and 8 of BK's primary sequence (74,(99)(100)(101)(102). Peptides such as DArg[Hyp3, (74,(99)(100)(101)103) and in vivo (101,102,104,105).…”

Section: New Generation Bz Receptor Antagonistsmentioning

confidence: 99%

“…Peptides such as DArg[Hyp3, (74,(99)(100)(101)103) and in vivo (101,102,104,105). Furthermore, these peptides, unlike some [DPhe7]-BK analogues, exhibit no spasmogenic activity in isolated smooth muscle (74, 10 1, 103).…”

Section: New Generation Bz Receptor Antagonistsmentioning

confidence: 99%

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Biochemical and Molecular Pharmacology of Kinin Receptors

Farmer

Burch²

1992

Annu. Rev. Pharmacol. Toxicol.

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202

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Threonine6-bradykinin: Conformational study of a flexible peptide in dimethyl sulfoxide by NMR and ensemble calculations

et al. 1996

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The conformation of the natural peptide threonine6 (Thr6)‐bradykinin, Arg1‐Pro2‐Pro3‐Gly4‐Phe5‐Thr6‐Pro7‐Phe8‐Arg9, was investigated in DMSO by nmr spectroscopy and computer simulations. The structural analysis of the Thr6‐peptide is made particularly interesting by the fact that despite the high sequence homology with native bradykinin (only one conservative substitution: Ser6/Thr6) there is a marked and significant difference in the biological profiles of the two peptides. The nmr spectra indicate a relatively flexible structure with the presence of an N‐terminal turn. Standard distance geometry calculations failed to produce structures in accord with the experimental observations; the resulting structures are indeed too rigid and conformationally restricted for the nmr data. The results of ensemble calculations reveal conformational changes occurring rapidly on the nmr time scale and allow for the establishment of a series of disordered conformations, prevalently extended with a partially populated turn in residues 2–5, which when considered together, as an average, fulfill the experimental restraints. The structural characterization of (Thr6)‐bradykinin supports the hypothesis of the significant role of the residue at position 6 on both conformation as well as biological activities and suggests a N‐terminal turn as a possible bioactive conformation. © 1997 John Wiley & Sons, Inc. Biopoly 40: 561–569, 1996

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Probing the bradykinin receptor: mapping the geometric topography using ethers of hydroxyproline in novel peptides

Cited by 83 publications

References 17 publications

Oral antinociception and oedema inhibition produced by NPC 18884, a non-peptidic bradykinin B2 receptor antagonist

Oral antinociception and oedema inhibition produced by NPC 18884, a non-peptidic bradykinin B2 receptor antagonist

Biochemical and Molecular Pharmacology of Kinin Receptors

Threonine6-bradykinin: Conformational study of a flexible peptide in dimethyl sulfoxide by NMR and ensemble calculations

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