| Synthesis and biological activity of oxytocin analogues containing unnatural amino acids in position 9: structure activity study. | |
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MedLine Citation:
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PMID: 19885720 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Vassiliki Magafa; Lenka Borovicková; Jirina Slaninová; Paul Cordopatis |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-11-03 |
Journal Detail:
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Title: Amino acids Volume: 38 ISSN: 1438-2199 ISO Abbreviation: Amino Acids Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-04-28 Completed Date: 2010-08-16 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9200312 Medline TA: Amino Acids Country: Austria |
Other Details:
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Languages: eng Pagination: 1549-59 Citation Subset: IM |
Affiliation:
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Laboratory of Pharmacognosy and Chemistry of Natural Products, Department of Pharmacy, University of Patras, 26500, Patras, Greece. magafa@upatras.gr |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acids
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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:
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0/Amino Acids; 50-56-6/Oxytocin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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