Bis-penicillamine enkephalins possess highly improved specificity toward delta opioid receptors (original) (raw)

1983, Proceedings of the National Academy of Sciences

The conformationally restricted, cyclic, disulfide-containing, enkephalin analogs [2-D-penicillamine, 5-L-penicdillamine]enkephalin ([D-Pen2,L-Pen']enkephalin) and [2-D-penicillamine, 5-D-penicillamine]enkephalin ([D-Pen D-Pen lenkephalin) were synthesized by solid-phase methods. Selectivities of these analogs for a single class of opioid receptor were investigated by examining relative potencies in the mouse vas deferens assay, in which the functional receptor is the 6 receptor, versus the guinea pig ileum assay, in which the ,u receptor is the functional receptor, and by determining their relative abilities to displace the prototypical 6 receptor ligand [D-Ala2,D-Leu5]enkephalin and the prototypical IA receptor ligand naloxone from rat brain membrane preparations. Based on these comparisons [D-Pen L-Pen ]and [D-P ,D-Pen5]enkephalin exhibited 6 receptor selectivities of 1,088 and 3,164, respectively, in the bioassays, and 371 and 175, respectively, in the binding assays. Compared with the previously reported 6 receptor selective analogs,