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Bivalent Inhibition of Human β-Tryptase by Norbert Schaschke; Gabriele Matschiner; Frank Zettl; Ulf Marquardt; Andreas Bergner; Wolfram Bode; Christian P Sommerhoff; Luis Moroder is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Bivalent Inhibition of Human β-Tryptase about?

Background: Human L-tryptase is a mast cell specific trypsinlike serine protease that is thought to play a key role in the pathogenesis of diverse allergic and inflammatory disorders like asthma and psoriasis. The recently resolved crystal structure revealed that the enzymatically active tetramer consists of four quasi-identical monomers. The spatial display of the four identical active sites represents an ideal basis for the rational design of bivalent inhibitors. Results: Based on modeling experiments homobivalent inhibitors were constructed using (i) 6A,6D-dideoxy-6A,6D-diamino-Lcyclodextrin as a rigid template to bridge the space between the two pairs of identical active sites and (ii) 3-(aminomethyl)benzene as a headgroup to occupy the arginine/lysine specific S1 subsites. A comparative analysis of the inhibitory potencies of synthetic constructs that differ in size and type of the spacer between headgroup and template revealed that the construct contained two 3-(aminomethyl)benzenesulfonyl-glycine groups linked to the 6A,6D-diamino groups of L-cyclodextrin as an almost ideal bivalent inhibitor with a cooperativity factor of 1.9 vs. the ideal value of 2. The bivalent binding m

Who reads Bivalent Inhibition of Human β-Tryptase?

Author

Norbert Schaschke; Gabriele Matschiner; Frank Zettl; Ulf Marquardt; Andreas Bergner; Wolfram Bode; Christian P Sommerhoff; Luis Moroder

Publisher

Elsevier Science; Elsevier ; Cell Press; Elsevier BV (ISSN 1074-5521)

Published

2001

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)