Novel Peptide-Heterocycle Hybrids: Synthesis and Preliminary Studies on Calpain Inhibition

Abstract

New peptidic compounds, having peptide chains linked to bi- and tricyclic heterocycles (peptide-heterocycle hybrids), have been synthesized. The heterocyclic components are derivatives of partially reduced isoquinoline and pyrido[1,2-b]isoquinoline bearing α,β-unsaturated carbonyl functionalities. The heterocyclic compounds have been used as acylating agents in coupling reactions with short N-unprotected peptides. Based on our interest on potential calpain inhibitors, we have used short (2-4 amino acids) peptides with hydrophobic amino acids of the two enantiomeric series. We report preliminary studies on the inhibition of calpain, with some compounds having IC50 values in the nanomolar range.