Document Detail


Synthesis and biological activity of oxytocin analogues containing unnatural amino acids in position 9: structure activity study.
MedLine Citation:
PMID:  19885720     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We report the solid phase synthesis and some pharmacological properties of 24 oxytocin (OT) analogues. Basic modifications at position 9 (introduction of L- or D-beta-(2-thienyl)-alanine [L- or D-Thi], or L- or D-3-Pyridylalanine [L- or D-3-Pal]) were combined with D-tyrosine(OEthyl) [D-Tyr(Et)] or D-1-naphthylalanine [D-1-Nal] in position 2 and beta-mercaptopropionic acid (Mpa) in position 1 modifications in altogether 14 analogues. Additionally, 8 analogues having alpha-aminoisobutyric acid [Aib] or D-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (D-Tic) or diethylglycine (Deg) in position 9 and D-Tyr(Et) or D-1-Nal or D-Tic in position 2 and Mpa or Pen (beta beta-dimethylcysteine) in position 1 were prepared. Two of these analogues have one more modification in position 6, i.e. Pen. Furthermore, two analogues having Mpa in position 1 and D-Tyr(Et) or D-1-Nal in position 2 were prepared for comparison purposes. The analogues were tested for rat uterotonic activity in vitro, in the rat pressor assay and for binding affinity to human OT receptor. The analogue having the highest anti-oxytocic activity was [Mpa(1), D-Tyr(Et)(2), Deg(9)]OT (pA(2) = 8.68 +/- 0.26); this analogue was also selective.
Authors:
Vassiliki Magafa; Lenka Borovicková; Jirina Slaninová; Paul Cordopatis
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-11-03
Journal Detail:
Title:  Amino acids     Volume:  38     ISSN:  1438-2199     ISO Abbreviation:  Amino Acids     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-28     Completed Date:  2010-08-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9200312     Medline TA:  Amino Acids     Country:  Austria    
Other Details:
Languages:  eng     Pagination:  1549-59     Citation Subset:  IM    
Affiliation:
Laboratory of Pharmacognosy and Chemistry of Natural Products, Department of Pharmacy, University of Patras, 26500, Patras, Greece. magafa@upatras.gr
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MeSH Terms
Descriptor/Qualifier:
Amino Acids / chemistry*
Animals
Chromatography, High Pressure Liquid
Female
Humans
Oxytocin / analogs & derivatives*,  chemical synthesis,  pharmacology
Rats
Spectrometry, Mass, Electrospray Ionization
Structure-Activity Relationship
Chemical
Reg. No./Substance:
0/Amino Acids; 50-56-6/Oxytocin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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