Synthesis and opioid activities of stereoisomers and other D-amino acid analogs of methionine-enkephalin

D. H. Coy, A. J. Kastin, Andrew V Schally, O. Morin, N. G. Caron, F. Labrie, J. M. Walker, R. Fertel, G. G. Berntson, C. A. Sandman

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Abstract

A series of D-amino acid-substituted analogs of the opiate peptide, methionine5-enkephalin, were synthesized by solid-phase methods and tested for their abilities to inhibit electrically-evoked contractions of mouse vasa deferentia and to compete with tritiated enkephalin for opiate receptors on particulate fractions isolated from homogenates of rat brain. [D-Ala2]-enkephalin and [D-Ala2]-enkephalin amide were found to be the most potent peptides in both assay systems, being about 1000% active in the vas deferens bioassay and 120% and 150% active, respectively, in the stereospecific binding test relative to methionine5-enkephalin itself. In comparison, [D-Met5]-, [D-Tyr1]-, [D-Leu2]-, [D-Phe2]-, [D-Ala3]-, and [D-Phe4]-enkephalin had not more than 10% activity. The stabilization of the β-bend conformation of methionine5-enkephalin by the substitution of D-alanine in position 2 of the peptide chain may contribute to the high activities of the [D-Ala2]-analogs.

Original languageEnglish
Pages (from-to)632-638
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume73
Issue number3
DOIs
StatePublished - Dec 6 1976
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Coy, D. H., Kastin, A. J., Schally, A. V., Morin, O., Caron, N. G., Labrie, F., Walker, J. M., Fertel, R., Berntson, G. G., & Sandman, C. A. (1976). Synthesis and opioid activities of stereoisomers and other D-amino acid analogs of methionine-enkephalin. Biochemical and Biophysical Research Communications, 73(3), 632-638. https://doi.org/10.1016/0006-291X(76)90857-3