Mookhtiar K A, Marlowe C K, Bartlett P A, Van Wart H E
Biochemistry. 1987 Apr 7;26(7):1962-5. doi: 10.1021/bi00381a026.
A series of phosphonamidates has been synthesized and shown to inhibit human neutrophil collagenase. The compounds all have sequences patterned after the cleavage site in the alpha 1(I) chain of type I collagen, except that the carbonyl group of the Gly residue in subsite P1 has been replaced by a P(= O)(OH) group (abbreviated GlyP). As the central GlyP-Leu unit is lengthened in the N- and C-terminal directions, in accordance with the cleavage sequence found in collagen, inhibition is systematically improved. The best inhibitor is Cbz-GlyP-Leu-Ala-Gly, which inhibits competitively with a KI value of 14 microM. These phosphonamidates are thought to be acting as transition-state analogues.
