Decapeptide Agonists of Human C5a

The Relationship between Conformation and Spasmogenic and Platelet Aggregatory Activities

Sam D. Sanderson, Leonid Kirnarsky, Simon Sherman, Julia A. Ember, Angela M. Finch, Stephen M. Taylor

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

A series of decapeptide analogues corresponding to the C-terminal region of human C5a anaphylatoxin (C5a65-74) was synthesized with residue substitutions to restrict conformational flexibility in the C-terminus. These conformationally constrained peptides behaved as agonists of C5a in spasmogenic assays (smooth muscle contraction in human fetal artery, guinea pig ileum, and guinea pig lung parenchyma) as well as guinea pig platelet aggregation. There were significant correlations in the potencies of these peptides between the various assays. A structure-function analysis led to the identification of a preferred backbone conformation that correlated with the expression of these biological responses. These backbone structural motifs were consistent with a helix-like conformation for residues 65-69, an elongated structure for residues 70-71, and a β-turn of either type II or type V for residues (71)72-74. The most potent of these agonists expressed almost 5% if the potency of natural C5a.

Original languageEnglish (US)
Pages (from-to)3171-3180
Number of pages10
JournalJournal of Medicinal Chemistry
Volume37
Issue number19
DOIs
StatePublished - Sep 1 1994

Fingerprint

Guinea Pigs
Blood Platelets
Anaphylatoxins
Peptides
Muscle Contraction
Platelet Aggregation
Ileum
Smooth Muscle
Arteries
Lung

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Decapeptide Agonists of Human C5a : The Relationship between Conformation and Spasmogenic and Platelet Aggregatory Activities. / Sanderson, Sam D.; Kirnarsky, Leonid; Sherman, Simon; Ember, Julia A.; Finch, Angela M.; Taylor, Stephen M.

In: Journal of Medicinal Chemistry, Vol. 37, No. 19, 01.09.1994, p. 3171-3180.

Research output: Contribution to journalArticle

Sanderson, Sam D. ; Kirnarsky, Leonid ; Sherman, Simon ; Ember, Julia A. ; Finch, Angela M. ; Taylor, Stephen M. / Decapeptide Agonists of Human C5a : The Relationship between Conformation and Spasmogenic and Platelet Aggregatory Activities. In: Journal of Medicinal Chemistry. 1994 ; Vol. 37, No. 19. pp. 3171-3180.
@article{65e07fbbaaeb4840a9469b57cff60bef,
title = "Decapeptide Agonists of Human C5a: The Relationship between Conformation and Spasmogenic and Platelet Aggregatory Activities",
abstract = "A series of decapeptide analogues corresponding to the C-terminal region of human C5a anaphylatoxin (C5a65-74) was synthesized with residue substitutions to restrict conformational flexibility in the C-terminus. These conformationally constrained peptides behaved as agonists of C5a in spasmogenic assays (smooth muscle contraction in human fetal artery, guinea pig ileum, and guinea pig lung parenchyma) as well as guinea pig platelet aggregation. There were significant correlations in the potencies of these peptides between the various assays. A structure-function analysis led to the identification of a preferred backbone conformation that correlated with the expression of these biological responses. These backbone structural motifs were consistent with a helix-like conformation for residues 65-69, an elongated structure for residues 70-71, and a β-turn of either type II or type V for residues (71)72-74. The most potent of these agonists expressed almost 5{\%} if the potency of natural C5a.",
author = "Sanderson, {Sam D.} and Leonid Kirnarsky and Simon Sherman and Ember, {Julia A.} and Finch, {Angela M.} and Taylor, {Stephen M.}",
year = "1994",
month = "9",
day = "1",
doi = "10.1021/jm00045a023",
language = "English (US)",
volume = "37",
pages = "3171--3180",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "19",

}

TY - JOUR

T1 - Decapeptide Agonists of Human C5a

T2 - The Relationship between Conformation and Spasmogenic and Platelet Aggregatory Activities

AU - Sanderson, Sam D.

AU - Kirnarsky, Leonid

AU - Sherman, Simon

AU - Ember, Julia A.

AU - Finch, Angela M.

AU - Taylor, Stephen M.

PY - 1994/9/1

Y1 - 1994/9/1

N2 - A series of decapeptide analogues corresponding to the C-terminal region of human C5a anaphylatoxin (C5a65-74) was synthesized with residue substitutions to restrict conformational flexibility in the C-terminus. These conformationally constrained peptides behaved as agonists of C5a in spasmogenic assays (smooth muscle contraction in human fetal artery, guinea pig ileum, and guinea pig lung parenchyma) as well as guinea pig platelet aggregation. There were significant correlations in the potencies of these peptides between the various assays. A structure-function analysis led to the identification of a preferred backbone conformation that correlated with the expression of these biological responses. These backbone structural motifs were consistent with a helix-like conformation for residues 65-69, an elongated structure for residues 70-71, and a β-turn of either type II or type V for residues (71)72-74. The most potent of these agonists expressed almost 5% if the potency of natural C5a.

AB - A series of decapeptide analogues corresponding to the C-terminal region of human C5a anaphylatoxin (C5a65-74) was synthesized with residue substitutions to restrict conformational flexibility in the C-terminus. These conformationally constrained peptides behaved as agonists of C5a in spasmogenic assays (smooth muscle contraction in human fetal artery, guinea pig ileum, and guinea pig lung parenchyma) as well as guinea pig platelet aggregation. There were significant correlations in the potencies of these peptides between the various assays. A structure-function analysis led to the identification of a preferred backbone conformation that correlated with the expression of these biological responses. These backbone structural motifs were consistent with a helix-like conformation for residues 65-69, an elongated structure for residues 70-71, and a β-turn of either type II or type V for residues (71)72-74. The most potent of these agonists expressed almost 5% if the potency of natural C5a.

UR - http://www.scopus.com/inward/record.url?scp=0028081049&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028081049&partnerID=8YFLogxK

U2 - 10.1021/jm00045a023

DO - 10.1021/jm00045a023

M3 - Article

VL - 37

SP - 3171

EP - 3180

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 19

ER -