European Journal of Medicinal Chemistry 2010-10-01

Synthesis and activity of endomorphin-2 and morphiceptin analogues with proline surrogates in position 2.

Cesare Giordano, Anna Sansone, Annalisa Masi, Gino Lucente, Pasqualina Punzi, Adriano Mollica, Francesco Pinnen, Federica Feliciani, Ivana Cacciatore, Peg Davis, Josephine Lai, Shou-Wu Ma, Frank Porreca, Victor Hruby

Index: Eur. J. Med. Chem. 45 , 4594-600, (2010)

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Abstract

The opioid agonists endomorphins (Tyr-Pro-Trp-Phe-NH(2); EM1 and Tyr-Pro-Phe-Phe-NH(2); EM2) and morphiceptin (Tyr-Pro-Phe-Pro-NH(2)) exhibit an extremely high selectivity for mu-opioid receptor. Here a series of novel EM2 and morphiceptin analogues containing in place of the proline at position 2 the S and R residues of beta-homologues of proline (HPro), of 2-pyrrolidinemethanesulphonic acid (HPrs) and of 3-pyrrolidinesulphonic acid (betaPrs) have been synthesized and their binding affinity and functional activity have been investigated. The highest micro-receptor affinity is shown by [(S)betaPrs(2)]EM2 analogue (6e) which represents the first example of a beta-sulphonamido analogue in the field of opioid peptides.Copyright © 2010 Elsevier Masson SAS. All rights reserved.