Synthesis of the diastereomers of β-Me-Tyr and β-Me-Phe and their effect on the biological properties of the delta opioid receptor antagonist TIPP

Els Mannekens, Dirk Tourwé, Sylvia Vanderstichele, Trang Nguyen Thi Diem, Géza Tóth, A. Péter, Nga N. Chung, Peter W. Schiller

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

In order to influence side-chain conformations and to increase the μ-agonist properties of the δ-selective opioid receptor δ-antagonist H-Tyr-Tic-Phe-Phe-NH2, residues Tyr1, Phe3 and Phe4 were replaced by their β-methyl-substituted stereoisomers. Synthesis of β-Me-Tyr was carried out in a stereoselective way. Incorporation of the modified amino acids was performed by SPPS. Receptor binding data and GPI and MVD bioassays were obtained for all stereoisomers, in general showing equal or slightly increased potencies. In the [(R,S)β-Me-Phe3]analogue, the introduction of the β-methyl substituent restores signal transduction.

Original languageEnglish
Pages (from-to)190-192
Number of pages3
JournalLetters in Peptide Science
Volume2
Issue number3-4
DOIs
Publication statusPublished - Nov 1995

Fingerprint

Signal transduction
delta Opioid Receptor
Stereoisomerism
Narcotic Antagonists
Bioassay
Conformations
Amino acids
phenylalanylphenylalanine
Biological Assay
Signal Transduction
Amino Acids
tyrosyl-1,2,3,4-tetrahydro-3-isoquinolinecarbonyl-phenylalanyl-phenylalanine
stable plasma protein solution
2-tyrosyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid

Keywords

  • β-Methyl amino acids
  • Boc strategy
  • Opioid peptide analogues
  • SPPS

ASJC Scopus subject areas

  • Biochemistry

Cite this

Synthesis of the diastereomers of β-Me-Tyr and β-Me-Phe and their effect on the biological properties of the delta opioid receptor antagonist TIPP. / Mannekens, Els; Tourwé, Dirk; Vanderstichele, Sylvia; Diem, Trang Nguyen Thi; Tóth, Géza; Péter, A.; Chung, Nga N.; Schiller, Peter W.

In: Letters in Peptide Science, Vol. 2, No. 3-4, 11.1995, p. 190-192.

Research output: Contribution to journalArticle

Mannekens, Els ; Tourwé, Dirk ; Vanderstichele, Sylvia ; Diem, Trang Nguyen Thi ; Tóth, Géza ; Péter, A. ; Chung, Nga N. ; Schiller, Peter W. / Synthesis of the diastereomers of β-Me-Tyr and β-Me-Phe and their effect on the biological properties of the delta opioid receptor antagonist TIPP. In: Letters in Peptide Science. 1995 ; Vol. 2, No. 3-4. pp. 190-192.
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AU - Vanderstichele, Sylvia

AU - Diem, Trang Nguyen Thi

AU - Tóth, Géza

AU - Péter, A.

AU - Chung, Nga N.

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