A5006767310- Peptidase Inhibition and Analysis
- Chemical Synthesis and Analysis
- Protease and Inhibitor Mechanisms
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Computational Drug Discovery Methods
- Enzyme Structure and Function
- Mast cells and histamine
- Blood Coagulation and Thrombosis Mechanisms
- Click Chemistry and Applications
- Synthesis and Catalytic Reactions
- Psoriasis: Treatment and Pathogenesis
- Synthesis and Biological Evaluation
- Chemical synthesis and pharmacological studies
- Enzyme Production and Characterization
- Protein Structure and Dynamics
- Bacterial Genetics and Biotechnology
- Signaling Pathways in Disease
- Synthesis and biological activity
- Glycosylation and Glycoproteins Research
- Asthma and respiratory diseases
- Hemoglobin structure and function
- Polyamine Metabolism and Applications
- Digestive system and related health
- Protein Tyrosine Phosphatases
- Bioactive Compounds and Antitumor Agents
Johnson & Johnson (United States)
2005-2025
Janssen (United States)
2011-2022
Springhouse
2011-2022
Baylor College of Medicine
1990-1997
Howard Hughes Medical Institute
1990-1997
South College
1995
Sterling Research Group (United States)
1994
Rice University
1991
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCrystallographic evidence of a large ligand-induced hinge-twist motion between the two domains maltodextrin binding protein involved in active transport and chemotaxisAndrew J. Sharff, Lynn E. Rodseth, John C. Spurlino, Florante A. QuiochoCite this: Biochemistry 1992, 31, 44, 10657–10663Publication Date (Print):November 1, 1992Publication History Published online1 May 2002Published inissue 1 November...
HDM2 binds to an alpha-helical transactivation domain of p53, inhibiting its tumor suppressive functions. A miniaturized thermal denaturation assay was used screen chemical libraries, resulting in the discovery a novel series benzodiazepinedione antagonists HDM2-p53 interaction. The X-ray crystal structure improved bound reveals their alpha-helix mimetic properties. These optimized molecules increase transcription p53 target genes and decrease proliferation cells expressing wild-type p53.
Abstract The X‐ray crystal structure of a 19 kDa active fragment human fibroblast collagenase has been determined by the multiple isomorphous replacement method and refined at 1.56 Å resolution to an R ‐factor 17.4%. current includes bound hydroxamate inhibitor, 88 waters three metal atoms (two zincs calcium). overall topology enzyme, comprised five stranded β‐sheet α‐helices, is similar thermolysin‐like metalloproteinases. There are some important differences between thermolysin families...
Aberrant activation of matrix metalloproteinases (MMPs) is a common feature pathological cascades observed in diverse disorders, such as cancer, fibrosis, immune dysregulation, and neurodegenerative diseases. MMP-9, particular, highly dynamically regulated several processes. Development MMP inhibitors has therefore been an attractive strategy for therapeutic intervention. However, long history failed clinical trials demonstrated that broad-spectrum have limited utility, which spurred the...
The cFMS proto-oncogene encodes for the colony-stimulating factor-1 receptor, a receptor-tyrosine kinase responsible differentiation and maturation of certain macrophages. Upon binding its ligand autophosphorylates, dimerizes, induces phosphorylation downstream targets. We report novel crystal structure unphosphorylated in complex with two members different classes drug-like protein inhibitors. exhibits typical bi-lobal fold, activation loop DFG motif are found to be canonical inactive...
The retinoic acid receptor-related orphan receptor gamma t (RORγt) is a nuclear transcription factor expressed in both innate and adaptive immune cells, driving Th17 cell differentiation IL-17 production. IL-23/IL-17 pathway implicated autoimmune inflammatory diseases, biologics that target signaling are efficacious the treatment of psoriasis psoriatic arthritis. RORγt, at core this pathway, represents an attractive opportunity for small-molecule intervention; however, combining high...
In this study, structure-based drug design of matrix metalloproteinase inhibitors [human fibroblast collagenase (HFC), human stromelysin (HFS), and neutrophil (HNC)] was utilized in the development potent hydroxamates which contain novel, heteroatom-based modifications P1' group. A series containing a butyramide group resulted nanomolar selective HNC inhibitor as well dual HFS/HNC inhibitor. Benzylic ethers with four- or five-carbon methylene linker position also produced inhibition...
Activated factor XI (FXIa) inhibitors are promising novel anticoagulants with low bleeding risk compared current anticoagulants. The discovery of potent FXIa good oral bioavailability has been challenging. Herein, we describe our effort, utilizing nonclassical interactions to improve potency, cellular permeability, and by enhancing the binding while reducing polar atoms. Beginning literature-inspired pyridine N-oxide-based inhibitor 1, imidazole linker was first replaced a pyrazole moiety...