[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. Simultaneous replacement of glycine by D-ornithine and C-terminal carboxyl amidation resulted in the potent analog whose selectivity toward the mu-receptors was 113 times as high as that of leucine-enkephalin. D-ornithine side chain prolongation by means of the attachment of some amino acid residues (methionine, leucine, proline, asparagine) led to the original branched enkephalin analogs. Studies of their binding activity showed that the best branched analog was only 27 times more selective for mu-vs delta-opiate receptors.
Inkina
N M
NM
Rozental'
G F
GF
D000818:Animals; D004745:Enkephalins / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D008297:Male; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D009952:Ornithine; D011869:Radioligand Assay; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism*; D017465:Receptors, Opioid, delta / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism
D004745:Enkephalins; D009842:Oligopeptides; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D009952:Ornithine
Issledovanie profilia retseptornoĭ selektivnosti ukorochennykh analogov énkefalina, soderzhashchikh D-ornitin vo vtorom polozhenii molekuly.