Novel peptide-heterocycle hybrids:synthesis and preliminary studies on calpain inhibition

摘要

New peptidic componds,having peptide chains linked to bi-and tricyclic heteorcycles (peptide-heterocycle hybrids),have been synthesized.The heterocyclic components are derivatives of partially reduced isoquinoline and pyridol[1,2-b]isoquinoline bearing alpha,beta-unsaturated carbonyl functionalities.The heterocyclic compounds have been used as acylating agents in coupling reactions with short N-unprotected peptides.Basedonour interest onpotential calpain inhibitors,we have used short (2-4 amino acids) peptides with hydrophobic amino acids of the two enantiomeric series.Wereport preliminary studies on the inhibition of calpain,with some compounds having IC_(50) values in the nanomolar range.