Mercaptoimidazolylpropionic acid hydrobromide. Inhibition of tadpole collagenase and related properties.
A mercapto analogue of histidine (1), (RS)-2-mercapto-3-(5-imidazolyl)propionic acid (2), was prepared by treatment of (RS)-2-bromo-3-(5-imidazolyl)propionic acid with trithiocarbonate. Decomposition of the resulting intermediate with hydrochloric acid followed by Sephadex G-15 chromatography permitted isolation of 2 as a hydrobromide complex having unusual stability and properties as evidenced by IR and 1H NMR data. The potency of this complex in inhibiting tissue (Rana catesbiana) collagenase was estimated by radial diffusion assay. The amount of 2 required to produce 50% inhibition was 3.8 +/- 1.5 mM compared to 8.7 +/- 2.5 mM for cysteine. Preliminary tests of oxygen susceptibility, mutagenicity, and toxicity suggest that this substance may warrant study as a therapeutic agent for control of collagenase-linked corneal ulcerations.
D000818:Animals; D001001:Anura; D001412:Bacillus subtilis / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D006639:Histidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity; D066298:In Vitro Techniques; D007814:Larva / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D003012:Microbial Collagenase / Q000037:antagonists & inhibitors*; D009153:Mutagens / Q000138:chemical synthesis; D010084:Oxidation-Reduction; D011892:Rana catesbeiana; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity
D009153:Mutagens; D013438:Sulfhydryl Compounds; D006639:Histidine; C017488:2-mercapto-3-(5-imidazolyl)propionic acid; D003012:Microbial Collagenase