| Abstract
| - Many proteinases, including gelatinase B/MMP-9, fulfillcrucial regulatory or effector functions in disease statesand may be pharmacologically targeted by specific inhibitors. Denatured collagen type II provides one of the bestgelatinase B substrates, and the characteristics of itscleavage were employed to define the requirements of anovel optimal substrate probe. A synthetic fluorescentderivative was used for the development of a new high-throughput technology for the selection of inhibitors onthe principles of sensitivity of confocal fluorescence detection, resolution capacity of capillary electrophoresis, andmultichannel power of DNA sequencers. Combinatorialchemical synthesis of a library of peptide-based inhibitors,library deconvolution, high-throughput screening, isolation, and mass spectrometric techniques enabled us toidentify a novel single-peptide gelatinase B inhibitor. Anotable finding is that the in vitro-selected inhibitormimics many of the characteristics of the evolution-selected MMP propeptide sequence.
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