Robert L Martin

Novel indolactam-based inhibitors of matrix metalloproteinases

Abstract Potent collagenase inhibitors incorporating a novel indolactam macrocycle, which are accessible by the intramolecular alkylation of N-t-Boc-L-Trp-NH(CH 2 ) 6 OTs under phase transfer conditions, show enhanced activity compared to their acyclic analogs.

Solid-phase synthesis of Di- and tripeptidic hydroxamic acids as inhibitors of procollagen C-proteinase

A solid-phase approach to the rapid synthesis of di- and tripeptide-like hydroxamic acids is presented. These compounds are shown to be potent inhibitors of procollagen C-proteinase (PCP).

Amino acid derived sulfonamide hydroxamates as inhibitors of procollagen C-proteinase: solid-phase synthesis of ornithine analogues.

A discussion of the solid-phase synthesis of ornithine derived sulfonamide hydroxamic acids is illustrated. These analogues are shown to be potent, non-peptide inhibitors of procollagen C-proteinase (PCP).

Human Placental Trophoblasts Secrete a Disintegrin Metalloproteinase Very Similar to the Insulin-Like Growth Factor Binding Protein-3 Protease in Human Pregnancy Serum1

During the course of human pregnancy, there is a marked increase in insulin-like growth factor (IGF) binding protein (IGFBP)-3 protease activity in maternal serum that is first evident at 6 weeks of gestation, persists through term, and returns to nonpregnancy levels by day 5 postpartum. This protease activity cleaves IGFBP-3 into smaller fragments that have markedly reduced affinity for the IGFs. To date, the precise identity and cellular origin of the pregnancy-associated serum IGFBP-3 protease have not been established. To investigate whether placental and/or decidual tissues, which uniquely develop during pregnancy, may be sources of the pregnancy-associated serum IGFBP protease, we examined the secretion of IGFBP-3 protease in vitro by isolated human cytotrophoblasts or fibroblasts from second trimester placentae and by in vitro decidualized human endometrial stromal cells. Cytotrophoblasts were either cultured alone, which favors aggregation and fusion, or cocultured with decidualized endometrial st...

Novel inhibitors of procollagen C-Proteinase. Part 2: glutamic acid hydroxamates☆

Glutamic acid derived hydroxamates were identified as potent and selective inhibitors of procollagen C-proteinase, an essential enzyme for the processing of procollagens to fibrillar collagens. Such compounds have potential therapeutic application in the treatment of fibrosis.

Amino acid derived sulfonamide hydroxamates as inhibitors of procollagen C-proteinase. Part 2: Solid-phase optimization of side chains

Optimization of the amino acid side chain and the N-alkyl group of the sulfonamide of amino acid derived sulfonamide hydroxamates is discussed. The solid-phase synthesis of these potent inhibitors of procollagen C-proteinase (PCP) is presented. In addition, novel carboxylic acid sulfonamides were discovered to be PCP inhibitors.

Novel inhibitors of procollagen C-terminal proteinase. Part 1: diamino Acid hydroxamates.

The parallel synthesis of novel inhibitors of procollagen C-terminal proteinase is described. The synthetic strategy allowed for the facile synthesis of a large number of side-chain diversified diamino acid hydroxamates, of which the D-diaminopropionic acid derivatives were shown to be single digit nanomolar PCP inhibitors.