[Synthesis of a cyclic enkephalin analog with prolonged action].
A cyclic analog of enkephalin, cyclo(Lys-Tyr-DMet-Gly-Phe-Pro-) and two corresponding linear hexapeptides with lysine residue on the N- and C-termini of the pentapeptide sequence, Lys-Tyr-DMet-Gly-Phe-Pro and Tyr-DMet-Gly-Phe-Pro-Lys were synthesized by classical and solid phase methods of peptide chemistry. The cyclic analog exhibited significantly prolonged analgesic effect, evaluated by the "tail pinch" method after intracysternal injection to mice. The cycloanalog also had a weak influence on the peripheral opiate receptors of the isolated segment of guinea pig iliac intestine. Addition of the lysine residue to the N-terminus of the pentapeptide sequence enhanced by an order of magnitude the selectivity of binding of the analog with opiate receptors of mu-type.
Bobrova
I V
IV
Myshliakova
N A
NA
Papsuevich
O S
OS
Vosekalna
I A
IA
Mekshun
E I
EI
D000595:Amino Acid Sequence; D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D002942:Circular Dichroism; D003692:Delayed-Action Preparations; D004745:Enkephalins / Q000138:chemical synthesis* / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000494:pharmacology; D011957:Receptors, Opioid / Q000187:drug effects
D000700:Analgesics; D003692:Delayed-Action Preparations; D004745:Enkephalins; D010456:Peptides, Cyclic; D011957:Receptors, Opioid; C094141:cyclo(lysyl-tyrosyl-methionyl-glycyl-phenylalanyl-prolyl)
Sintez tsiklicheskogo analoga énkefalina prolongirovannogo deĭstviia.