scholarly journals A new class of protein sensor links spirochete pleomorphism, persistence, and chemotaxis

2022 ◽  
Author(s):  
Alise R. Muok ◽  
Kurni Kurniyati ◽  
Davi R. Ortega ◽  
Flory Olsthoorn ◽  
Adam Sidi Mabrouk ◽  
...  
Keyword(s):  
Small Molecule ◽  
Protein Modeling ◽  
Treponema Denticola ◽  
Direct Link ◽  
Body Formation ◽  
New Class ◽  
And Behaviors ◽  
Improved Model ◽  
Protein Sensor ◽  
Behavioral Assays

Pathogenic spirochetes can alter their morphologies and behaviors to infect and survive within their hosts. Previous reports demonstrate that the formation of so-called round bodies and biofilms, and chemotaxis are involved in spirochete pathogenesis. Here, in the spirochete Treponema denticola, we report a direct link between these cellular states that involves a new class of protein sensor (CheWS) with hitherto unclear function. Using cryo-EM methods, protein modeling, bioinformatics, genetics methods, and behavioral assays we demonstrate that spirochetes regulate these behaviors in response to the small molecule s-adenosylmethionine (SAM) via a SAM sensor that is anchored to chemotaxis arrays. CheWS influences chemotaxis, biofilm and round body formation under non-stressed conditions by a novel sporulation-like mechanism. Taken together, we establish an improved model for round body formation, we discovered a direct link between this SAM sensor and changes in cellular states, as well as characterized a new sensor class involved in chemotaxis.

Small-Molecule Antagonists of CCR5 and CXCR4: A Promising New Class of Anti-HIV-1 Drugs

2004 ◽  
Vol 10 (17) ◽  
pp. 2041-2062 ◽  
Author(s):  
Christoph Seibert ◽  
Thomas Sakmar
Keyword(s):  
Small Molecule ◽  
New Class ◽  
Anti Hiv ◽  
Hiv 1

Recent Development of Small Molecule Glutaminase Inhibitors

2018 ◽  
Vol 18 (6) ◽  
pp. 432-443 ◽  
Author(s):  
Minsoo Song ◽  
Soong-Hyun Kim ◽  
Chun Young Im ◽  
Hee-Jong Hwang
Keyword(s):  
Small Molecule ◽  
Cell Metabolism ◽  
Phase 1 ◽  
Vital Role ◽  
Glutamine Metabolism ◽  
Inhibition Mechanism ◽  
Tumor Cell Growth ◽  
X Ray ◽  
New Class ◽  
Preclinical And Clinical Studies

Glutaminase (GLS), which is responsible for the conversion of glutamine to glutamate, plays a vital role in up-regulating cell metabolism for tumor cell growth and is considered to be a valuable therapeutic target for cancer treatment. Based on this important function of glutaminase in cancer, several GLS inhibitors have been developed in both academia and industry. Most importantly, Calithera Biosciences Inc. is actively developing the glutaminase inhibitor CB-839 for the treatment of various cancers, and it is currently being evaluated in phase 1 and 2 clinical trials. In this review, recent efforts to develop small molecule glutaminase inhibitors that target glutamine metabolism in both preclinical and clinical studies are discussed. In particular, more emphasis is placed on CB-839 because it is the only small molecule GLS inhibitor being studied in a clinical setting. The inhibition mechanism is also discussed based on X-ray structure studies of thiadiazole derivatives present in glutaminase inhibitor BPTES. Finally, recent medicinal chemistry efforts to develop a new class of GLS inhibitors are described in the hopes of providing useful information for the next generation of GLS inhibitors.

scholarly journals New diagonal micropolarizer arrays designed by an improved model in fourier domain

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jia Hao ◽  
Yan Wang ◽  
Kui Zhou ◽  
Xiaochang Yu ◽  
Yiting Yu
Keyword(s):  
Stokes Parameters ◽  
Fourier Domain ◽  
Extended Model ◽  
Reconstruction Accuracy ◽  
Polarization Imaging ◽  
New Class ◽  
Reconstruction Quality ◽  
Improved Design ◽  
Improved Model

AbstractThe design of micropolarizer array (MPA) patterns in Fourier domain provides an efficient approach to reconstruct and investigate the polarization information. Inspired by Alenin’s works, in this paper, we propose an improved design model to cover both 2 × N MPAs and other original MPAs, by which an entirely new class of MPA patterns is suggested. The performance of the new patterns is evaluated through Fourier domain analysis and numerical simulations compared with the existing MPAs. Particularly, we analyze the reconstruction accuracy of the first three Stokes parameters and degree of linear polarization (DoLP) in detail. The experimental results confirm that the 2 × 2 × 2 MPA provides the highest reconstruction quality of s0, s1, s2 and DoLP in terms of quantitative measures and visual quality, while the 3 × 3 diagonal MPA achieves the state-of-the-art best results in case of single-snapshot systems. The guidance of this extended model and new diagonal MPAs show its massive potential for the division of focal plane (DoFP) polarization imaging applications.

scholarly journals Ventromorphins: A New Class of Small Molecule Activators of the Canonical BMP Signaling Pathway

2017 ◽  
Vol 12 (9) ◽  
pp. 2436-2447 ◽  
Author(s):  
Jamie R. Genthe ◽  
Jaeki Min ◽  
Dana M. Farmer ◽  
Anang A. Shelat ◽  
Jose A. Grenet ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Small Molecule ◽  
Bmp Signaling ◽  
New Class

ChemInform Abstract: Amidinohydrazones as Guanidine Bioisosteres: Application to a New Class of Potent, Selective and Orally Bioavailable, Non-amide-based Small-Molecule Thrombin Inhibitors.

ChemInform ◽  
2010 ◽  
Vol 31 (18) ◽  
pp. no-no
Author(s):  
Richard M. Soll ◽  
Tianobao Lu ◽  
Bruce Tomczuk ◽  
Carl R. Illig ◽  
Cynthia Fedde ◽  
...  
Keyword(s):  
Small Molecule ◽  
Thrombin Inhibitors ◽  
New Class ◽  
Orally Bioavailable

scholarly journals Screening for Caspase-3 Inhibitors: A New Class of Potent Small-Molecule Inhibitors of Caspase-3

2006 ◽  
Vol 11 (3) ◽  
pp. 277-285 ◽  
Author(s):  
Ilya Okun ◽  
Sergei Malarchuk ◽  
Elena Dubrovskaya ◽  
Alexander Khvat ◽  
Sergey Tkachenko ◽  
...  
Keyword(s):  
Small Molecule ◽  
High Throughput Screening ◽  
Caspase 3 ◽  
Small Molecule Inhibitors ◽  
High Potency ◽  
New Class ◽  
Mechanistic Analysis ◽  
Compound Collection ◽  
Induced Apoptosis

From the authors'650,000 compound collection, they have selected approximately 15,000 potential small-molecule protease inhibitors, which were subjected to high-throughput screening against caspase-3. The screening yielded a series of hits that belong to 11 different scaffolds. Based on the structure of one of the hits, a new class of the small-molecule inhibitors with a double electrophilicwarhead, 8-sulfonyl-pyrrolo[3,4-c]quinoline-1,3-diones (SPQ), was synthesized and tested in follow-up mechanistic and antiapoptosis assays. Mechanistic analysis of a representative compound of this class, CD-001-0011, showed that the compound exhibited a high potency (IC 50 = 130 nM), was reversible though noncompetitive, and had a broad selectivity profile to other caspases belonging to groups I to III. The compound was effective in preventing staurosporineinduced apoptosis in a few cell lines and retinoic acid–induced apoptosis in zebrafish.

Identification of a new class of small molecule C5a receptor antagonists

2010 ◽  
Vol 20 (2) ◽  
pp. 662-664 ◽  
Author(s):  
Jack J. Chen ◽  
Derek C. Cole ◽  
Greg Ciszewski ◽  
Kimberly Crouse ◽  
John W. Ellingboe ◽  
...  
Keyword(s):  
Small Molecule ◽  
Receptor Antagonists ◽  
C5a Receptor ◽  
New Class

scholarly journals A new class of small molecule estrogen receptor-alpha antagonists that overcome anti-estrogen resistance

Oncotarget ◽  
2015 ◽  
Vol 6 (38) ◽  
pp. 40388-40404 ◽  
Author(s):  
Yongxian Ma ◽  
Anju Preet ◽  
York Tomita ◽  
Eliseu De Oliveira ◽  
Li Zhang ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Small Molecule ◽  
Estrogen Receptor Alpha ◽  
Receptor Alpha ◽  
New Class

The entrepreneurial director

2007 ◽  
Vol 10 (2) ◽  
pp. 51-57
Author(s):  
Bruce C. Sherony
Keyword(s):  
Board Of Directors ◽  
Small Businesses ◽  
Behavior Patterns ◽  
Entrepreneurial Success ◽  
Checks And Balances ◽  
Helpful Tool ◽  
The Board Of Directors ◽  
And Behaviors ◽  
Improved Model

The argument that the board of directors can be a helpful tool for entrepreneurships and small businesses derives from the rationale for using boards from both a macro and a micro perspective.Society depends on boards to provide overall checks and balances in the running of businesses.This could not be more evident from the role of the board in Enron’s collapse (U.S. Senate 2002). The boardʼs value to the entrepreneur is found in the application of the micro perspective.Two sets of recommendations are developed to formulate an improved model of directorship actions and behaviors. First, duties and responsibilities of the board of directors are expanded to help guide entrepreneurs.Second, five unique behavior patterns are then proposed that can be particularly helpful in carrying out the duties and activities of the board for guiding entrepreneurial success.

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