TY - JOUR
T1 - Synthesis and opioid activities of stereoisomers and other D-amino acid analogs of methionine-enkephalin
AU - Coy, D. H.
AU - Kastin, A. J.
AU - Schally, A. V.
AU - Morin, O.
AU - Caron, N. G.
AU - Labrie, F.
AU - Walker, J. M.
AU - Fertel, R.
AU - Berntson, G. G.
AU - Sandman, C. A.
PY - 1976/12/6
Y1 - 1976/12/6
N2 - 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.
AB - 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.
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U2 - 10.1016/0006-291X(76)90857-3
DO - 10.1016/0006-291X(76)90857-3
M3 - Article
C2 - 1008880
AN - SCOPUS:0017124216
VL - 73
SP - 632
EP - 638
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -