A novel 3-step enantioselective synthesis of pyrenylalanine with subsequent incorporation into opioid, CCK, and melanotropin ligands

Isabel Alves, Scott Cowell, Yeon Sun Lee, Xuejun Tang, Peg Davis, Frank Porreca, Victor J Hruby

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Pyrene possesses unique spectroscopic properties such as a high quantum yield, a long half-life in the excited state, and the ability to form excimers when in proximity to each other in the excited state. These properties allow pyrenylalanine, which is a pyrene moiety incorporated into an amino acid, to be used as a fluorescent probe in peptides and proteins [J. Chem. Soc. Perkin Trans. 2 (1995) 1133; J. Am. Chem. Soc. 111 (1989) 6790; J. Chem. Soc. Perkin Trans. 2 (1997) 517]. The common route for the synthesis of pyrenylalanine involves 5 steps [Macromolecules 18 (1985) 882], with subsequent separation of the two isomers by recrystallization. This paper reports a novel 3-step asymmetric synthesis of pyrenylalanine with high enantioselectivity, good yields, and facile isomer purification. After synthesis, pyrenylalanine was incorporated into a series of opioid, CCK, and melanotropin peptide ligands in order to study the effects of aromaticity, lipophilicity, and steric properties on their potency and efficacy at their corresponding biological receptors. The change in binding and efficacy of the labeled ligands as compared to the unlabeled ligands demonstrates the possible role of lipophilicity/aromaticity in the binding and signal transduction of the ligand-receptor interaction.

Original languageEnglish (US)
Pages (from-to)335-340
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume318
Issue number2
DOIs
StatePublished - May 28 2004

Fingerprint

Melanocyte-Stimulating Hormones
Opioid Analgesics
Ligands
Excited states
Isomers
Signal transduction
Peptides
Enantioselectivity
Quantum yield
Macromolecules
Fluorescent Dyes
Purification
Half-Life
Signal Transduction
Crystallization
Amino Acids
Proteins
pyrene

Keywords

  • Cholecystokinin
  • Enantioselective amino acid synthesis
  • Melanocortin
  • Opioid
  • Pyrenylalanine

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

A novel 3-step enantioselective synthesis of pyrenylalanine with subsequent incorporation into opioid, CCK, and melanotropin ligands. / Alves, Isabel; Cowell, Scott; Lee, Yeon Sun; Tang, Xuejun; Davis, Peg; Porreca, Frank; Hruby, Victor J.

In: Biochemical and Biophysical Research Communications, Vol. 318, No. 2, 28.05.2004, p. 335-340.

Research output: Contribution to journalArticle

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