Linked Life Data

2162330

Source:http://linkedlifedata.com/resource/pubmed/id/2162330

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1990-7-20
pubmed:abstractText
Based on structure-activity relationships of the potent alpha-MSH agonist, Ac-Nle4-Asp5-His6-D-Phe7-Arg8-Trp9-Lys10-NH2, several analogs of the general formula Ac-Nle4-Asp5-Waa6-Xaa7-Yaa8-Zaa9-Lys10+ ++-NH2 were synthesized and tested on frog and lizard skin bioassays for their possible inhibitory actions against alpha-MSH on melanocyte stimulation. When Waa6 = Trp, Xaa7 = D-Phe, Yaa8 = Nle and Zaa = Trp, a highly potent alpha-MSH antagonist, Ac-Nle-Asp-Trp-D-Phe-Nle-Trp-Lys-NH2, with selectivity on the frog skin alpha-MSH receptor system (pA2 = 8.4) was obtained. However, several modifications in the amino acid sequence of the peptide resulted in a complete loss of antagonistic activity and a recovery of very weak agonistic action. The following changes in the amino acid sequence of the peptide were examined; His or D-Trp for Waa, L-Phe for Xaa, Arg, Ala or Pro for Yaa, and D-Trp for Zaa. All resulted in full agonists with no antagonistic activity. In addition, lactam cyclization between the Asp5 and Lys10 side chains in the antagonist gave a full agonist and a complete loss of antagonistic activity. Efforts to develop a rational approach for the design of selective alpha-MSH antagonists for the frog skin alpha-MSH receptor will be discussed.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0367-8377
pubmed:author
pubmed:issnType
Print
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
228-34
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
Design, synthesis, and biological activities of a potent and selective alpha-melanotropin antagonist.
pubmed:affiliation
Department of Chemistry, University of Arizona, Tucson.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.