Abstract
alpha-Aminoalkylphosphonate di(chlorophenyl) esters and (alpha-aminoalkyl)phenylphosphinate phenylesters have been tested as irreversible inhibitors of human neutrophil elastase, porcine pancreatic elastase and chymotrypsin, serine proteases important in biochemical processes. Peptidyl derivatives of diphenyl (alpha-aminoalkyl) phosphonates have previously been shown to be potent and specific inhibitors of serine proteases at low concentrations. Addition of a halogen to the phenoxy group of the inhibitors should make the leaving group more electrophilic, and thus more reactive. Peptide phosphonate inhibitors with chlorine in the meta- or para-positions of the phenoxy ester moiety were synthesized and shown to be potent inhibitors of elastase. Tripeptide phosphonates are more potent inhibitors than dipeptide phosphonates, however, addition of the halogen did not increase the inhibitory potency of these phosphonates with elastase compared to the non-halogenated phosphonates. In the case of chymotrypsin, the halogenated phenoxy esters were more reactive, possibly due to an alternate binding mode. The novel (alpha-aminoalkyl)phenylphosphinate phenylesters were poor inhibitors of serine proteases.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
