In situ assembly of enzyme inhibitors using extended tethering

2003 ◽  
Vol 21 (3) ◽  
pp. 308-314 ◽  
Author(s):  
Daniel A. Erlanson ◽  
Joni W. Lam ◽  
Christian Wiesmann ◽  
Tinh N. Luong ◽  
Robert L. Simmons ◽  
...  
Keyword(s):  
Enzyme Inhibitors

Titelbild: In Situ Assembly and Screening of Enzyme Inhibitors with Surface-Tension Microarrays (Angew. Chem. 41/2009)

2009 ◽  
Vol 121 (41) ◽  
pp. 7589-7589
Author(s):  
Laurent Mugherli ◽  
Olga N. Burchak ◽  
Larissa A. Balakireva ◽  
Aline Thomas ◽  
François Chatelain ◽  
...  
Keyword(s):  
Surface Tension ◽  
Enzyme Inhibitors

scholarly journals Development and Validation of a Simple Cell-Based Fluorescence Assay for Dipeptidyl Peptidase 1 (DPP1) Activity

2010 ◽  
Vol 16 (1) ◽  
pp. 36-43 ◽  
Author(s):  
Bob Thong ◽  
James Pilling ◽  
Edward Ainscow ◽  
Raj Beri ◽  
John Unitt
Keyword(s):  
Cell Sorting ◽  
Enzyme Inhibitors ◽  
Dipeptidyl Peptidase ◽  
Fluorescence Assay ◽  
Enzyme Assays ◽  
Fluorogenic Substrates ◽  
Intracellular Degradation ◽  
Dipeptidyl Aminopeptidase ◽  
Development And Validation

Dipeptidyl peptidase 1 (DPP1) (EC 3.4.14.1; also known as cathepsin C, cathepsin J, dipeptidyl aminopeptidase, and dipeptidyl aminotransferase) is a lysosomal cysteinyl protease of the papain family involved in the intracellular degradation of proteins. Isolated enzyme assays for DPP1 activity using a variety of synthetic substrates such as dipeptide or peptide linked to amino-methyl-coumarin (AMC) or other fluorophores are well established. There is, however, no report of a simple whole-cell-based assay for measuring lysosomal DPP1 activity other than the use of flow cytometry (fluorescence-activated cell sorting) or the use of invasive activity-based probes or the production of physiological products such as neutrophil elastase. The authors investigated a number of DPP1 fluorogenic substrates that have the potential to access the lysosome and enable the measurement of DPP1 enzyme activity in situ. They describe the development and evaluation of a simple noninvasive fluorescence assay for measuring DPP1 activity in fresh or cryopreserved human THP-1 cells using the substrate H-Gly-Phe-AFC (amino-fluoro-coumarin). This cell-based fluorescence assay can be performed in a 96-well plate format and is ideally suited for determining the cell potency of potential DPP1 enzyme inhibitors.

Tetrabutylammonium Fluoride-Mediated Rapid Alkylation Reaction in Microtiter Plates for the Discovery of Enzyme Inhibitors in Situ

ChemBioChem ◽  
2005 ◽  
Vol 6 (12) ◽  
pp. 2176-2180 ◽  
Author(s):  
Chung-Yi Wu ◽  
Ashraf Brik ◽  
Sheng-Kai Wang ◽  
Yu-Hsien Chen ◽  
Chi-Huey Wong
Keyword(s):  
Enzyme Inhibitors ◽  
Alkylation Reaction ◽  
Microtiter Plates ◽  
Tetrabutylammonium Fluoride

In Situ Click Chemistry:  Enzyme Inhibitors Made to Their Own Specifications

2004 ◽  
Vol 126 (40) ◽  
pp. 12809-12818 ◽  
Author(s):  
Roman Manetsch ◽  
Antoni Krasiński ◽  
Zoran Radić ◽  
Jessica Raushel ◽  
Palmer Taylor ◽  
...  
Keyword(s):  
Click Chemistry ◽  
Enzyme Inhibitors

scholarly journals Steroidal ferrocenes as potential enzyme inhibitors of the estrogen biosynthesis

2020 ◽  
Vol 71 (3) ◽  
pp. 249-264
Author(s):  
Bianka Edina Herman ◽  
János Gardi ◽  
János Julesz ◽  
Csaba Tömböly ◽  
Eszter Szánti-Pintér ◽  
...  
Keyword(s):  
Enzyme Inhibitors ◽  
Inhibitory Effect ◽  
Ferrocene Derivatives ◽  
17Β Estradiol ◽  
Inhibitory Potential ◽  
Estrogen Biosynthesis

Abstract The potential inhibitory effect of diverse triazolyl-ferrocene steroids on key enzymes of the estrogen biosynthesis was investigated. Test compounds were synthesized via copper-catalyzed cycloaddition of steroidal azides and ferrocenyl-alkynes using our efficient methodology published previously. Inhibition of human aromatase, steroid sulfatase (STS) and 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) activities was investigated with in vitro radiosubstrate incubations. Some of the test compounds were found to be potent inhibitors of the STS. A compound bearing ferrocenyl side chain on the C-2 displayed a reversible inhibition, whereas C-16 and C-17 derivatives displayed competitive irreversible binding mechanism toward the enzyme. 17α-Triazolyl-ferrocene derivatives of 17β-estradiol exerted outstanding inhibitory effect and experiments demonstrated a key role of the ferrocenyl moiety in the enhanced binding affinity. Submicromolar IC50 and Ki parameters enroll these compounds to the group of the most effective STS inhibitors published so far. STS inhibitory potential of the steroidal ferrocenes may lead to the development of novel compounds able to suppress in situ biosynthesis of 17β-estradiol in target tissues.

In situ Generation of Irreversible Enzyme Inhibitors

1972 ◽  
Vol 237 (71) ◽  
pp. 53-53 ◽  
Author(s):  
ROBERT R. RANDO
Keyword(s):  
Enzyme Inhibitors ◽  
In Situ Generation

In Situ Assembly and Screening of Enzyme Inhibitors with Surface-Tension Microarrays

2009 ◽  
Vol 121 (41) ◽  
pp. 7775-7780 ◽  
Author(s):  
Laurent Mugherli ◽  
Olga N. Burchak ◽  
Larissa A. Balakireva ◽  
Aline Thomas ◽  
François Chatelain ◽  
...  
Keyword(s):  
Surface Tension ◽  
Enzyme Inhibitors

scholarly journals A biocompatible stapling reaction for in situ generation of constrained peptides

2020 ◽  
Author(s):  
Richard Morewood ◽  
Christoph Nitsche
Keyword(s):  
Enzyme Inhibitors ◽  
Biochemical Assays ◽  
Constrained Peptides ◽  
In Situ Generation ◽  
Peptide Stapling

A synthetically straightforward and biocompatible peptide-stapling strategy that can be used directly in biochemical assays to identify constrained enzyme inhibitors.

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