New Potent Biphalin Analogues Containing P-fluoro-L-phenylalanine at the 4,4' Positions and Non-hydrazine Linkers

Overview

Journal Amino Acids

Specialty Biochemistry

Date 2010 Oct 7

PMID 20924622

Citations 8

Authors

Adriano Mollica

Francesco Pinnen

Federica Feliciani

Azzurra Stefanucci

Gino Lucente

Peg Davis

Frank Porreca

Shou-Wu Ma

Josephine Lai

Victor J Hruby

Affiliations

Soon will be listed here.

Abstract

We report the synthesis and the biological evaluation of two new analogues of the potent dimeric opioid peptide biphalin. The performed modification is based on the replacement of two key structural elements of the native biphalin, namely: the hydrazine bridge which joins the two palindromic moieties and the phenylalanine residues at the 4,4' positions of the backbone. The new analogues 9 and 10 contain 1,2-phenylenediamine and piperazine, respectively, in place of the hydrazidic linker and p-fluoro-L-phenylalanine residues at 4 and 4' positions. Binding values are: Kμ(i)=0.51 nM and Kδ(i)=12.8 nM for compound 9, Kμ(i)=0.09 nM and Kδ(i)=0.11 nM for analogue 10.

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