Cyclic enkephalins receptor selectivity

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. 

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. 

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

In contract to these eompoynds, the myre conformatlonally constrained [d Pen, D-Cys ]-, [D-Pen. Cys ]-, [0 -Pen, D -Pen ]-, and C)-Pen. Pen ]-enkephalins exhibit exceptional 6 receptor selectivity. Conformational differences associated with the Pen residues appear to be responsible for the high receptor selectivity. Finally, a series of cyclic retro-Inverso enkephalins have been designed to incorporate favorable conformational restriction and Increased resistance to enzymatic degradation. 

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