Document Detail

Identification and in Vivo and in Vitro Characterization of Long Acting and Melanocortin 4 Receptor (MC4-R) Selective α-Melanocyte-Stimulating Hormone (α-MSH) Analogues.
MedLine Citation:
PMID:  22335602     Owner:  NLM     Status:  Publisher    
We report in vitro and in vivo data of new α-melanocyte-stimulating hormone (α-MSH) analogues which are N-terminal modified with a long chain fatty acid derivative. While keeping the pharmacophoric motif (d-Phe-Arg-Trp) fixed, we tried to improve selectivity and physicochemical parameters like solubility and stability of these analogues by replacing amino acids further away from the motif. Receptor specific changes in binding affinity to the melanocortin receptors were observed between the acetyl derivatives and the fatty acid analogues. Furthermore, amino acids at the N-terminal of α-MSH (Ser-Tyr-Ser) not considered to be part of the pharmacophore were found to have an influence on the MC4/MC1 receptor selectivity. While the acetyl analogues have an in vivo effect for around 7 h, the long chain fatty acid analogues have an effect up to 48 h in an acute feeding study in male Sprague-Dawley rats after a single subcutaneous administration.
Kilian Conde-Frieboes; Henning Thøgersen; Jesper F Lau; Ulrich Sensfuss; Thomas K Hansen; Leif Christensen; Jane Spetzler; Helle B Olsen; Cecilia Nilsson; Kirsten Raun; Kirsten Dahl; Birgit S Hansen; Birgitte S Wulff
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-2-24
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  -     ISSN:  1520-4804     ISO Abbreviation:  -     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-2-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Protein & Peptide Chemistry, Novo Nordisk, Novo Nordisk Park, 2760 Måløv, Denmark.
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