Anti-inflammatory activity of α-MSH(11-13) analogs: Influences of alteration in stereochemistry

M. E. Hiltz, A. Catania, J. M. Lipton

Research output: Contribution to journalArticlepeer-review

Abstract

D-Amino acid substitutions in the anti-inflammatory/antipyretic Ac-α-MSH(11-13)-NH2 tripeptide of Ac-α-MSH(1-13)-NH2 were made and the altered peptides were injected in mice treated with picryl chloride. Ear swelling, measured 3 and 6 h after application of the irritant, was reduced by IP injections of Ac-α-MSH(11-13)-NH2, in confirmation of previous observations. Ac-[D-Lys11]α-MSH(11-13)-NH2 effected similar anti-inflammatory activity but Ac-[D-Pro12]α-MSH(11-13)-NH2 was inactive. Ac-[D-Val13]α-MSH(11-13)-NH2 and Ac-[D-Lys11,D-Val13]α-MSH(11-13)-NH2 generally had greater anti-inflammatory activity than the parent tripeptide molecule; the dose-response relations exhibited the bell-shaped characteristics seen previously with MSH peptides. The results indicate that the L-Pro12 is essential for the anti-inflammatory activity of Ac-α-MSH(11-13)-NH2 whereas the L-Lys11 is not. D-Val13 substitution increased anti-inflammatory activity approximately four-fold over Ac-α-MSH(11-13)-NH2. These results provide new structure-activity relationships of the anti-inflammatory Ac-α-MSH(11-13)-NH2 molecule. The data support the developing idea that α-MSH and its COOH-terminal fragments modulate host responses, perhaps by antagonizing the actions of cytokines.

Original languageEnglish
Pages (from-to)767-771
Number of pages5
JournalPeptides
Volume12
Issue number4
DOIs
Publication statusPublished - 1991

Keywords

  • Inflammation
  • Modulation of host responses
  • Neuropeptide
  • α-Melanocyte stimulating hormone

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Cellular and Molecular Neuroscience

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