Hydroxamate derivatives of substrate-analogous peptides containing aminomalonic acid are potent inhibitors of matrix metalloproteinases.
D Krumme, H Wenzel, H Tschesche
Index: FEBS Lett. 436(2) , 209-212, (1998)
Full Text: HTML
Abstract
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 collagenase (cdMMP-8) were determined. The most effective inhibitor synthesized exhibits Ki values of 2 x 10(-6) M (cdMMP-8) and 5 x 10(-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 P1-P1'-peptide bond shows a high resistance to cleavage by the proteinases.
Related Compounds
Related Articles:
Heterocyclizations, XIV. 1,3,5,7,-Tetraoxoperhydroimidazo[1,5-c]imidazole, a Novel Bridgehead Nitrogen Ureide Capuano L, et al.
[Chem. Ber. 107(10) , 3237-3245, (1974)]
Alpha-alkylcysteines as inhibitors for carboxypeptidase A. Synthesis, evaluation, and implication for inhibitor design strategy. Lee HS and Kim DH.
[Bull. Korean Chem. Soc. 23(4) , 593-598, (2002)]
Synthesis of Nitro Compounds Starting with Dialkyl Aminomalonates. Ishchenko MA, et al.
[Russ. J. Org. Chem. 37(2) , 194-197, (2001)]
Oxindole as starting material in organic synthesis. Ziarani GM, et al.
[ARKIVOC 1 , 470-535, (2013)]