MATRIX METALLOPROTEINASE INHIBITORS CONTAINING AMINOMALONIC ACID DERIVATIVES AND PEPTIDE BACKBONE MODIFIED DERIVATIVES THEREOF

摘要

Novel peptides containing the sequence -Pro-Leu-Ama(NHOH)- were synthesized and characterized by spectroscopic techniques. Their inhibitory properties towards the activated form of native human gelatinase B (MMP-9) and the catalytic domain of neutrophil colagenase (cdMMP-8) were determined. The most effective inhibitor synthesized exhibits Ki values of 2x10-6 M (cdMMP-8) and 5x10-9 M(MMP-9) thus attaining interesting discrimination between the tested metalloproteinases. A most important feature of this type of inhibitor is its peptide nature making the compounds similar to natural substrates. In spite of the peptide character of the inhibitors synthesized, the P¿1?-P1'-peptide bond shows a high resistance to cleavage by the proteinases.