[Receptor selectivity profile of short enkephalin analogs containing D-ornithine at the second position of the molecule].

The radioreceptor binding assay using a membrane fraction from the rat brain was applied to study binding activity and opiate receptor selectivity of truncated enkephalin analogs (with a free or modified C-terminal carboxyl group) bearing D-ornithine at the second position. D-ornithine introduction does not lead to the increase of mu-receptor selectivity as is proposed by the Schwyzer membrane selection model. Some additional modifications (C-terminal amidation or ornithine side chain acetylation) of tetrapeptide molecule were required to reach mu-selectivity.

[The effect of modification of the carboxyl group in short D-arginine 2-containing enkephalin analogs on their affinity and selectivity for opiate receptors].

Radioreceptor binding assay using a membrane fraction from the rat brain was applied to study [D-Arg2, Leu5] enkephalin and two series of its analogues truncated at the C-terminus with a free or modified carboxyl group: tetra- and tripeptide amides and ethyl esters. The affinity to mu-specific opiate receptor subtype of the N-terminal [D-Arg2] tetrapeptide ethyl ester was 44 times as high as that of the tripeptide with a free carboxyl, and thus the ester retained up to 10% of leucine-enkephalin binding potency. However, a comparable esterification of the carboxyl group in the N-terminal [D-Arg2] tripeptide led to a 6-fold reduction in its affinity to mu-receptors.

[Structural-functional relations of short analogs of enkephalin].

The similarity of action of narcotic analgesics and opioid peptides is due to activation of a common opiate receptor as the primary step in initiating biochemical chains responsible for diverse morphine-like effects. The most widely used assays for opioid and analgesic activities are presented and evaluated. Approximately 180 short enkephalin analogues (di-, tri- and tetrapeptides), described in the literature, are systematized and their opioid and systemic analgesic activities compared with methionine-enkephalin and morphine as the reference compounds, respectively.