Truncation studies of alpha-melanotropin peptides identify tripeptide analogues exhibiting prolonged agonist bioactivity.
Truncation studies of alpha-melanotropin peptides identify tripeptide analogues exhibiting prolonged agonist bioactivity: PEPTIDES 17(6) 995-1002, 1996.-Systematic analysis of fragment derivatives of the superpotent alpha-MSH analogue. Ac-Ser.Tyr-Ser-Nle4-Glu- His-DPhe7-Arg-Trp-Gly-Lys-Pro-Val-NH2(NDP-MSH), led to the discovery of tripeptide agonists possessing prolonged bioactivity in the frog skin assay. Of particular significance to this discovery was Ac-DPhe-Arg-DTrp-NH2, which was the most potent tripeptide in this series exhibiting sustained melanotropic activity. Different pharmacophore models appear to exist that are dependent on the substructure and stereochemistry of the MSH(6-9) "active site." The tripeptides Ac-DPhe-Arg-Trp-NH2, Ac-DPhe-Arg-DTrp-NH2, and Ac-DPhe-DArg-Trp-NH2 stereo-chemical combinations require only Phe7-Xaa8-Trp9, whereas Ac-DPhe-DArg-DTrp-NH2, Ac-Phe-Arg-DTrp-NH2, and Ac-Phe-Arg-Trp-NH2 additionally require His4 for minimal biological activity. Ac-DPhe-Arg-DTrp-NH2 represents a novel prototype lead for the development of MSH-based peptidomimetic agonists.
Haskell-Luevano
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C
Department of Chemistry, University of Arizona, Tucson 85721, USA.
Sawyer
T K
TK
Hendrata
S
S
North
C
C
Panahinia
L
L
Stum
M
M
Staples
D J
DJ
Castrucci
A M
AM
Hadley
M F
MF
Hruby
V J
VJ
D000595:Amino Acid Sequence; D000818:Animals; D001681:Biological Assay; D004305:Dose-Response Relationship, Drug; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011894:Rana pipiens; D011979:Receptors, Pituitary Hormone / Q000819:agonists*; D012867:Skin / Q000187:drug effects*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D000521:alpha-MSH / Q000031:analogs & derivatives* / Q000737:chemistry
D009842:Oligopeptides; D010446:Peptide Fragments; D011979:Receptors, Pituitary Hormone; D000521:alpha-MSH; C027756:MSH, 4-Nle-7-Phe-alpha-; C029446:MSH receptor