Enkephalins cyclic analogs

Lactam 36 was the first cyclic enkephalin analog prepared. It has a higher affinity for the p-opioid receptor than for the 8-receptor. The methylamine-bridged enkephalin (MABE) analog 37 exhibits nanomolar affinity for isolated p- and 8-receptors and in an in vivo (rat) thermal escape assay an ED50 of 0.027 pg was determined, as compared with an ED50 of 2.4 pg for morphine. ... 

DiMaio J, Schiller PW. A cyclic enkephalin analog with high in vitro opiate activity. Proc Natl Acad Sci USA 1980 77 7162-7166. 

DiMaio J, Nguyen TM-D, Lemieux C, Schiller PW. Synthesis and pharmacological characterization in vitro of cyclic enkephalin analogs effect of conformational constraints on opiate receptor selectivity. J Med Chem 1982 25 1432-1438. 

Berman JM, Goodman M, Nguyen TM-D, Schiller PW. Cyclic and acyclic partial retro-inverso enkephalins mu receptor selective enzyme resistant analogs. Biochem Biophys Res Commun 1983 115 864-870. 

Development of Cyclic Enkephalin Analogs with High Receptor SpecTn city--------------- ---------------------------------... 

Mosberg, H.I., Hurst, R., Hruby, V.J., Gee, K., Akiyama. K., Yamamura, H.I., Galligan, J.J., Burks, T.F. Cyclic penicillamine containing enkephalin analogs display profound delta receptor selectivities, Life Sci 1983, 33 Suppl. 1, 447-50. 

Fig. 3. Structure of a cyclic enkephalin analog designed by Schiller and co-workers (DiMaio el al., 1982).

Conformational Free Energies of Cyclic Enkephalin Analogs. ... 

Delta-selective enkephalin analogs were prepared by cyclizationthrough disulfide bond formation. (Cyclic enkephalin analogs containing D- or L-Cys residues in positions 2 and 5... 

As in the case of cyclic enkephalin analogs, conformationally constrained 6-selective peptides with the sequence Tyr-o-X-Phe were also prepared by cyclization through a disulfide bond. Cyclization between o-Cys in position 2 and D-Pen in position 4 yielded the tetrapep-tide derivative Tyr-cyc/o[D-Cys-Phe-D-Pen]-OH (JOM-13, 249), which contains a fairly... 

Various peptides from the enkephalin family, or analogs of these molecules, permeate through the blood-brain barrier at different rates, often by different mechanisms [49]. For example, D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (a cyclic peptide that binds to jU.-opioid receptors, in which Pen is penicillamine) permeates by diffusion only Tyr-D-Pen-Gly-Phe-D-Pen ([d-Penj -enkephalin, a cyclic Met-enkephalin analog that binds to 5-opioid receptors) permeates by diffusion and a saturable transport mechanism (Tyr-D-Ala-Gly-Phe-NH)2 (biphalin, a dimeric analog that is active at fx-... 

K. and Yamamura, H.I. (1983) Conformationally constrained cyclic enkephalin analogs with pronounced delta opioid receptor agonist selectivity. Life Sci. 32 2565-2569. 

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