PMID: 11325588Apr 28, 2001Paper

Bivalent inhibition of human beta-tryptase

Chemistry & Biology
Norbert SchaschkeL Moroder

Abstract

Human beta-tryptase is a mast cell specific trypsin-like 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. Based on modeling experiments homobivalent inhibitors were constructed using (i) 6A,6D-dideoxy-6A,6D-diamino-beta-cyclodextrin 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 beta-cyclodextrin as an almost ideal bivalent inhibitor with a cooperativity factor of 1.9 vs. the ideal value of 2. The bivalent binding mode is supported by the inhibitor/tetramer ratio of 2:1 r...Continue Reading

References

Jul 21, 1979·Journal of Theoretical Biology·H P Rappaport
Mar 1, 1992·Protein Science : a Publication of the Protein Society·D A Johnson, G J Barton
Oct 1, 1992·Biological Chemistry Hoppe-Seyler·J StürzebecherC P Sommerhoff
Mar 1, 1972·Immunochemistry·D M Crothers, H Metzger
Feb 2, 1996·The Journal of Biological Chemistry·J E HuntN Ghildyal
Aug 12, 1996·FEBS Letters·N SchaschkeL Moroder
Feb 1, 1996·Chemistry & Biology·L L Kiessling, N L Pohl
Jan 1, 1997·The European Respiratory Journal·P R JohnsonJ L Black
Jun 1, 1997·American Journal of Respiratory Cell and Molecular Biology·G H Caughey
Dec 5, 1998·Biochimica Et Biophysica Acta·K A LindstedtP T Kovanen
May 13, 1999·Proceedings of the National Academy of Sciences of the United States of America·G LoidlL Moroder
Jul 21, 1999·Proceedings of the National Academy of Sciences of the United States of America·L E BurgessK Koch
Sep 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·C P SommerhoffA Bergner
Oct 3, 1999·European Journal of Biochemistry·T SteinmetzerJ Stürzebecher
Dec 28, 1999·Bioorganic & Medicinal Chemistry Letters·S OnoT Kondo
Feb 16, 2000·Journal of Peptide Science : an Official Publication of the European Peptide Society·G LoidlL Moroder
Mar 10, 2000·Biochimica Et Biophysica Acta·C P SommerhoffH Fritz
Apr 13, 2000·Bioorganic & Medicinal Chemistry Letters·N SchaschkeL Moroder
Jul 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·W P Jencks

❮ Previous
Next ❯

Citations

Aug 7, 2002·Journal of Molecular Biology·Ulf MarquardtChristian Sommerhoff
Apr 18, 2002·Bioorganic & Medicinal Chemistry Letters·Norbert SchaschkeChristian P Sommerhoff
Jan 15, 2004·Biological Chemistry·Trevor SelwoodNorman M Schechter
Sep 14, 2010·International Journal of Peptide Research and Therapeutics·S P LiuR W Beuerman
Dec 9, 2004·Expert Opinion on Therapeutic Targets·Heather L HandlRobert J Gillies
Oct 27, 2009·Journal of Molecular Biology·Christian P SommerhoffHarald Kolmar
Feb 27, 2016·Chemistry : a European Journal·Mathieu L LepagePhilippe Compain
Jun 20, 2006·Current Opinion in Structural Biology·Younjoo Lee, Nicole S Sampson
Dec 14, 2004·Chembiochem : a European Journal of Chemical Biology·Norbert SchaschkeChristian P Sommerhoff
Sep 5, 2015·Organic & Biomolecular Chemistry·Nasreddine KanfarPascal Dumy
Aug 2, 2014·Chemistry : a European Journal·Sébastien G Gouin
Oct 31, 2007·Arthritis and Rheumatism·H S PalmerW R Ferrell
May 8, 2009·Organic & Biomolecular Chemistry·Roland J Pieters
Jun 2, 2005·Biopolymers·Knud J Jensen, Jesper Brask
Apr 15, 2010·Chembiochem : a European Journal of Chemical Biology·Jörg Scheuermann, Dario Neri
Apr 28, 2006·The FEBS Journal·Jenny Hallgren, Gunnar Pejler
Apr 18, 2019·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Philippe Compain
Aug 3, 2019·The European Respiratory Journal·Gunnar Pejler
Jul 1, 2015·Beilstein Journal of Organic Chemistry·Susanne Liese, Roland R Netz
Jul 25, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Florian SchiemannFrank Petersen
Sep 2, 2003·Organic & Biomolecular Chemistry·Jeroen van Ameijde, Rob M J Liskamp
Feb 15, 2020·Journal of Medicinal Chemistry·Sarah F GiardinaFrancis Barany
Oct 31, 2002·Journal of the American Chemical Society·Zhongsheng ZhangErkang Fan

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology
E M ErinT T Hansel
Current Pharmaceutical Design
Christian P Sommerhoff, Norbert Schaschke
Proceedings of the National Academy of Sciences of the United States of America
Christian P SommerhoffA Bergner
© 2021 Meta ULC. All rights reserved