Surface plasmon resonance imaging biosensor for cathepsin G based on a potent inhibitor: development and applications.

A specific surface plasmon resonance imaging (SPRI) array biosensor for the determination of the enzymatically active cathepsin G (CatG) has been developed. For this purpose, a specific interaction between an inhibitor immobilized onto a chip surface and CatG in an analyzed solution was used. The MARS-115 CatG peptidyl inhibitor containing the 1-aminoalkylphosphonate diaryl ester moiety at the C terminus and N-succinamide with a free carboxylic function was synthesized and covalently immobilized onto the gold chip surface via the thiol group (cysteamine).

Novel diphenyl esters of peptidyl alpha-aminoalkylphosphonates as inhibitors of chymotrypsin and subtilisin.

The activities of novel Cbz-N-protected alpha-aminophosphonic phenyl esters, analogs of leucine (1-15) and phenylalanine (17-29), which are substituted at the phenyl ester rings, as well as of their peptidic derivatives (31-43), were investigated for their inhibitory effects on chymotrypsin and subtilisin. The chemical nature and position of the examined substituents clearly demonstrated a strong structure-activity relationship. Among all synthesized compounds the most potent phosphonic-type inhibitors of subtilisin and chymotrypsin were identified, with k(2)/K(i) values 114,380 M(-1)s(-1) and 307,380 M(-1)s(-1), respectively.

New potent cathepsin G phosphonate inhibitors.

Cathepsin G is an enzyme with dual chymotrypsin and trypsin-like specificity. As a leukocyte proteinase it is involved in the early stages of the immune response. In this work the synthesis and inhibitory activity of diaryl phosphonic-type irreversible cathepsin G inhibitors are described.