Increased biological activity of dimers of oxymorphone and enkephalin: possible role of receptor crosslinking
Hazum, E.; Chang, K.J.; Leighton, H.J.; Lever, O.W.; Cuatrecasas, P.
Biochemical and Biophysical Research Communications 104(1): 347-353
1982
ISSN/ISBN: 0006-291X PMID: 6176227 Document Number: 188350
Four analogs of oxymorphone, oxymorphaminothylthiol, oxymorphaminoethyldisulfide, oxymorphaminoethyl-nitrobenzoic acid disulfide and oxymorphone thiazolidine, as well as the enkephalin analogs, enkephalin-thiol, Tyr-D-Ala-Gly-Phe-Leu-Lys (.epsilon.-NH)COCH2CH2SH and the enkephalin-dimer, [Tyr-D-Ala-Gly-Phe-Leu-Lys (.epsilon.NH)COCH2CH2S-]2, were examined for binding to enkephalin and morphine receptors. The analogs gained substantial affinity for enkephalin and lost affinity for morphine receptors. The affinity of the dimers of both opiates and enkephalins was slightly greater than that achieved by the corresponding thiol monomers. In the guinea pig ileum the dimeric analogs were much more active than the monomers. Receptor dimerization or cross-linking may be involved in the biological activity of opiates and opioid peptides.