Determination of structural elements related to the biological activities of a potent decapeptide agonist of human C5a anaphylatoxin

S. M. Vogen, O. Prakash, L. Kirnarsky, S. D. Sanderson, Simon Sherman

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Abstract

The structural features related to the biologic activities of a potent, response-selective decapeptide agonist of human C5a, YSFKPMPLaR (C5a65- 74, Y65, F67, P69, P71, D-Ala73), were identified by NMR analysis in H2O, DMSO and TFE. This investigation showed that the KPM residues in H2O and the SFKPM residues in DMSO exhibited an extended backbone conformation, whereas a twisted conformation was found in this region in TFE. In H2O, the C-terminal region (PLaR) adopted a distorted type II β-turn or a type II/V β-turn. In the type II/V β-turn, Leu72 exhibited a conformation typical of a type II β-turn, whereas D-Ala73 exhibited a conformation characteristic of a type V β-turn. Furthermore, a γ-turn involving residues LaR overlapped with the type II/V β-turn. In DMSO, the C-terminal region had the analogous turn- like motif (type II/V β-turn overlapping with γ-turn) found in H2O. In TFE, no β-turn motifs were formed by the PLaR residues. These turn-like motifs in the C-terminal region of the peptide in both H2O and DMSO were in agreement with the biologically important conformations predicted earlier by a structure-function analysis of a related panel of decapeptide analogs. The motifs determined by the NMR analysis of YSFKPMPLaR in H2O and DMSO may represent structural elements important for C5a agonist activity and thus can be used to design the next generation of C5a agonist, partial agonist and antagonist analogs.

Original languageEnglish (US)
Pages (from-to)74-84
Number of pages11
JournalJournal of Peptide Research
Volume54
Issue number1
DOIs
StatePublished - Jul 27 1999

Fingerprint

Anaphylatoxins
Dimethyl Sulfoxide
Bioactivity
Conformations
Polytetrafluoroethylene
Nuclear magnetic resonance
Peptides

Keywords

  • Agonist
  • Human C5a
  • Nuclear magnetic resonance
  • β-turn
  • γ-turn

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

Cite this

Determination of structural elements related to the biological activities of a potent decapeptide agonist of human C5a anaphylatoxin. / Vogen, S. M.; Prakash, O.; Kirnarsky, L.; Sanderson, S. D.; Sherman, Simon.

In: Journal of Peptide Research, Vol. 54, No. 1, 27.07.1999, p. 74-84.

Research output: Contribution to journalArticle

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AB - The structural features related to the biologic activities of a potent, response-selective decapeptide agonist of human C5a, YSFKPMPLaR (C5a65- 74, Y65, F67, P69, P71, D-Ala73), were identified by NMR analysis in H2O, DMSO and TFE. This investigation showed that the KPM residues in H2O and the SFKPM residues in DMSO exhibited an extended backbone conformation, whereas a twisted conformation was found in this region in TFE. In H2O, the C-terminal region (PLaR) adopted a distorted type II β-turn or a type II/V β-turn. In the type II/V β-turn, Leu72 exhibited a conformation typical of a type II β-turn, whereas D-Ala73 exhibited a conformation characteristic of a type V β-turn. Furthermore, a γ-turn involving residues LaR overlapped with the type II/V β-turn. In DMSO, the C-terminal region had the analogous turn- like motif (type II/V β-turn overlapping with γ-turn) found in H2O. In TFE, no β-turn motifs were formed by the PLaR residues. These turn-like motifs in the C-terminal region of the peptide in both H2O and DMSO were in agreement with the biologically important conformations predicted earlier by a structure-function analysis of a related panel of decapeptide analogs. The motifs determined by the NMR analysis of YSFKPMPLaR in H2O and DMSO may represent structural elements important for C5a agonist activity and thus can be used to design the next generation of C5a agonist, partial agonist and antagonist analogs.

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