Synthesis, opiate receptor affinity, and conformational parameters of [4-tryptophan]enkephalin analogues.
A series of analogues of the opioid peptide enkephalin with tryptophan substituted for phenylalanine in position 4 was synthesized by the solid-phase method. The [Trp4]enkephalin analogues and the corresponding [Phe4]enkephalin analogues displayed nearly parallel affinities in the opiate receptor binding assay throughout the series. In a conformational study fluorescence parameters were measured and intramolecular Tyr-Trp distances were estimated on the basis of resonance energy transfer experiments. No gross conformational differences were observed between analogues with widely differing opiate receptor affinity; however, small but significant changes in the intramolecular distance between the phenol ring and the indole moiety and/or in their relative orientation became apparent in some compounds. Identical intramolecular distances of 9.3 +/- 0.2 angstrom between the two aromatic rings were obtained with [Trp4,Met5]enkephalin, [Trp4,Leu5]enkephalin, and the N-terminal tetrapeptide comprised in the latter two analogues, indicating the existence of folded conformationas in 2 X 10(-5) M aqueous solution and demonstrating conformational analogy between these three peptides. The conformational parameters are discussed in relation to the observed affinities and the putative opiate receptor topography.
D000595:Amino Acid Sequence; D000818:Animals; D002531:Cerebellum / Q000378:metabolism; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004723:Endorphins / Q000138:chemical synthesis*; D004735:Energy Transfer; D004745:Enkephalins / Q000138:chemical synthesis* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008956:Models, Chemical; D008968:Molecular Conformation; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D014364:Tryptophan
D004723:Endorphins; D004745:Enkephalins; D011957:Receptors, Opioid; D014364:Tryptophan