Amino Acids

, Volume 38, Issue 5, pp 1549–1559 | Cite as

Synthesis and biological activity of oxytocin analogues containing unnatural amino acids in position 9: structure activity study

  • Vassiliki Magafa
  • Lenka Borovičková
  • Jiřina Slaninová
  • Paul Cordopatis
Original Article


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-β-(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 β-mercaptopropionic acid (Mpa) in position 1 modifications in altogether 14 analogues. Additionally, 8 analogues having α-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 (ββ-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 [Mpa1, d-Tyr(Et)2, Deg9]OT (pA2 = 8.68 ± 0.26); this analogue was also selective.


Oxytocin antagonists Position 9 Unnatural amino acids Biological activity Binding affinity 





β-Mercaptopropionic acid




α-Aminoisobutyric acid












1,2, 3, 4, -Tetrahydroisoquinoline-3-carboxylic acid


















Tetrabutylammonium fluoride


Trifluoroacetic acid


High-performance liquid chromatography


Electrospray ionization–mass spectrometry



Partial funding for this work was provided by research project No. Z40550506 of the Academy of Sciences of the Czech Republic.


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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Vassiliki Magafa
    • 1
  • Lenka Borovičková
    • 2
  • Jiřina Slaninová
    • 2
  • Paul Cordopatis
    • 1
  1. 1.Laboratory of Pharmacognosy and Chemistry of Natural Products, Department of PharmacyUniversity of PatrasPatrasGreece
  2. 2.Department of Antimicrobial Peptides, Institute of Organic Chemistry and BiochemistryAcademy of Sciences of Czech RepublicPrague 6Czech Republic

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