NMR analysis of a potent decapeptide agonist of human C5a anaphylatoxin

Shawn M. Vogen, Om Prakash, Leonid Kirnarsky, Sam D. Sanderson, Simon Sherman

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

A NMR investigation in H2O, TFE and DMSO of a conformationally constrained, potent decapeptide agonist of human C5a, YSFKDMPLaR (C5a65- 74, Y65, F67, P71, D-Ala73) showed that its N-terminal region (YSFKD) exhibited an extended backbone conformation in H2O and a more twisted conformation in both TFE/H2O (30:70, v/v; referred to as TFE) and DMSO. The C-terminal region (MPLaR) of the peptide adopted compact, turn-like structures. In H2O, the C-terminal region adopted a type II β-turn or a distorted type V/II β-turn involving residues PLaR. In the distorted type V/II β-turn, Leu72 exhibited a conformation typical of a type V β-turn, whereas D-Ala73 exhibited a conformation typical of a type II β-turn. The distorted type V/II β-turn overlapped with an inverse γ-turn involving residues MPL. In DMSO, the C-terminal region had the analogous inverse γ- turn and the VII β-turn found in H2O. In many of the DMSO structures, two inverse γ-turns in the MPL and PLa positions formed a double-inverse γ- turn. None of the turns observed in H2O were present in TFE. However, in TFE, the PLa residues formed an inverse γ-turn. Overall, the turn-like structural motifs in the C-terminal region of the peptide in both H2O and DMSO (but not in TFE) agreed with the biologically important conformations obtained earlier by the structure-function analysis of a panel of C5a agonist peptides. These motifs may represent key structural elements important for C5a agonist activity and may be used to design the next generation of C5a agonist and antagonist analogues.

Original languageEnglish (US)
Pages (from-to)226-234
Number of pages9
JournalJournal of Peptide Research
Volume51
Issue number3
StatePublished - Mar 24 1998

Fingerprint

Anaphylatoxins
Polytetrafluoroethylene
Dimethyl Sulfoxide
Nuclear magnetic resonance
Conformations
Peptides

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

Cite this

Vogen, S. M., Prakash, O., Kirnarsky, L., Sanderson, S. D., & Sherman, S. (1998). NMR analysis of a potent decapeptide agonist of human C5a anaphylatoxin. Journal of Peptide Research, 51(3), 226-234.

NMR analysis of a potent decapeptide agonist of human C5a anaphylatoxin. / Vogen, Shawn M.; Prakash, Om; Kirnarsky, Leonid; Sanderson, Sam D.; Sherman, Simon.

In: Journal of Peptide Research, Vol. 51, No. 3, 24.03.1998, p. 226-234.

Research output: Contribution to journalArticle

Vogen, SM, Prakash, O, Kirnarsky, L, Sanderson, SD & Sherman, S 1998, 'NMR analysis of a potent decapeptide agonist of human C5a anaphylatoxin', Journal of Peptide Research, vol. 51, no. 3, pp. 226-234.
Vogen SM, Prakash O, Kirnarsky L, Sanderson SD, Sherman S. NMR analysis of a potent decapeptide agonist of human C5a anaphylatoxin. Journal of Peptide Research. 1998 Mar 24;51(3):226-234.
Vogen, Shawn M. ; Prakash, Om ; Kirnarsky, Leonid ; Sanderson, Sam D. ; Sherman, Simon. / NMR analysis of a potent decapeptide agonist of human C5a anaphylatoxin. In: Journal of Peptide Research. 1998 ; Vol. 51, No. 3. pp. 226-234.
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abstract = "A NMR investigation in H2O, TFE and DMSO of a conformationally constrained, potent decapeptide agonist of human C5a, YSFKDMPLaR (C5a65- 74, Y65, F67, P71, D-Ala73) showed that its N-terminal region (YSFKD) exhibited an extended backbone conformation in H2O and a more twisted conformation in both TFE/H2O (30:70, v/v; referred to as TFE) and DMSO. The C-terminal region (MPLaR) of the peptide adopted compact, turn-like structures. In H2O, the C-terminal region adopted a type II β-turn or a distorted type V/II β-turn involving residues PLaR. In the distorted type V/II β-turn, Leu72 exhibited a conformation typical of a type V β-turn, whereas D-Ala73 exhibited a conformation typical of a type II β-turn. The distorted type V/II β-turn overlapped with an inverse γ-turn involving residues MPL. In DMSO, the C-terminal region had the analogous inverse γ- turn and the VII β-turn found in H2O. In many of the DMSO structures, two inverse γ-turns in the MPL and PLa positions formed a double-inverse γ- turn. None of the turns observed in H2O were present in TFE. However, in TFE, the PLa residues formed an inverse γ-turn. Overall, the turn-like structural motifs in the C-terminal region of the peptide in both H2O and DMSO (but not in TFE) agreed with the biologically important conformations obtained earlier by the structure-function analysis of a panel of C5a agonist peptides. These motifs may represent key structural elements important for C5a agonist activity and may be used to design the next generation of C5a agonist and antagonist analogues.",
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AU - Prakash, Om

AU - Kirnarsky, Leonid

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AU - Sherman, Simon

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