scholarly journals A chemical biology view of bioactive small molecules and a binder-based approach to connect biology to precision medicines

2018 ◽  
Author(s):  
Stuart L. Schreiber
Keyword(s):  
Small Molecules ◽  
Chemical Biology

scholarly journals Small molecules with big roles in microRNA chemical biology and microRNA-targeted therapeutics

RNA Biology ◽  
2019 ◽  
Vol 16 (6) ◽  
pp. 707-718 ◽  
Author(s):  
Rengen Fan ◽  
Chaocheng Xiao ◽  
Xinqiang Wan ◽  
Wenzhang Cha ◽  
Yufeng Miao ◽  
...  
Keyword(s):  
Small Molecules ◽  
Chemical Biology ◽  
Targeted Therapeutics

Target engagement approaches for pharmacological evaluation in animal models

2019 ◽  
Vol 55 (63) ◽  
pp. 9241-9250 ◽  
Author(s):  
James E. Kath ◽  
Aleksandra Baranczak
Keyword(s):  
Animal Models ◽  
Small Molecules ◽  
Chemical Biology ◽  
Target Engagement ◽  
Pharmacological Evaluation

We highlight recent applications of chemical biology approaches to measure target engagement of small molecules in animal models to support the nomination of clinical candidates.

scholarly journals From Phenotypic Hit to Chemical Probe: Chemical Biology Approaches to Elucidate Small Molecule Action in Complex Biological Systems

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5702
Author(s):  
Quentin T. L. Pasquer ◽  
Ioannis A. Tsakoumagkos ◽  
Sascha Hoogendoorn
Keyword(s):  
Small Molecules ◽  
Chemical Biology ◽  
Target Identification ◽  
Biologically Active ◽  
Phenotypic Screening ◽  
Biological Processes ◽  
Chemical Probes ◽  
Target Deconvolution ◽  
Cellular Target ◽  
Screening Approaches

Biologically active small molecules have a central role in drug development, and as chemical probes and tool compounds to perturb and elucidate biological processes. Small molecules can be rationally designed for a given target, or a library of molecules can be screened against a target or phenotype of interest. Especially in the case of phenotypic screening approaches, a major challenge is to translate the compound-induced phenotype into a well-defined cellular target and mode of action of the hit compound. There is no “one size fits all” approach, and recent years have seen an increase in available target deconvolution strategies, rooted in organic chemistry, proteomics, and genetics. This review provides an overview of advances in target identification and mechanism of action studies, describes the strengths and weaknesses of the different approaches, and illustrates the need for chemical biologists to integrate and expand the existing tools to increase the probability of evolving screen hits to robust chemical probes.

scholarly journals Challenges and Opportunities for Small Molecule Aptamer Development

2012 ◽  
Vol 2012 ◽  
pp. 1-20 ◽  
Author(s):  
Maureen McKeague ◽  
Maria C. DeRosa
Keyword(s):  
Molecular Recognition ◽  
Small Molecules ◽  
Small Molecule ◽  
Chemical Biology ◽  
Biological Functions ◽  
High Affinity ◽  
Challenges And Opportunities ◽  
Recognition Elements ◽  
Technical Challenges ◽  
Viable Approach

Aptamers are single-stranded oligonucleotides that bind to targets with high affinity and selectivity. Their use as molecular recognition elements has emerged as a viable approach for biosensing, diagnostics, and therapeutics. Despite this potential, relatively few aptamers exist that bind to small molecules. Small molecules are important targets for investigation due to their diverse biological functions as well as their clinical and commercial uses. Novel, effective molecular recognition probes for these compounds are therefore of great interest. This paper will highlight the technical challenges of aptamer development for small molecule targets, as well as the opportunities that exist for their application in biosensing and chemical biology.

scholarly journals Selective auxin agonists induce specific AUX/IAA protein degradation to modulate plant development

2019 ◽  
Vol 116 (13) ◽  
pp. 6463-6472 ◽  
Author(s):  
Thomas Vain ◽  
Sara Raggi ◽  
Noel Ferro ◽  
Deepak Kumar Barange ◽  
Martin Kieffer ◽  
...  
Keyword(s):  
Small Molecules ◽  
Chromatin Remodeling ◽  
Plant Development ◽  
Chemical Biology ◽  
Auxin Signaling ◽  
Transcriptional Repressors ◽  
Transport Inhibitor ◽  
Specific Subset ◽  
Protein Ligases ◽  
Indole 3 Acetic Acid

Auxin phytohormones control most aspects of plant development through a complex and interconnected signaling network. In the presence of auxin, AUXIN/INDOLE-3-ACETIC ACID (AUX/IAA) transcriptional repressors are targeted for degradation by the SKP1-CULLIN1-F-BOX (SCF) ubiquitin-protein ligases containing TRANSPORT INHIBITOR RESISTANT 1/AUXIN SIGNALING F-BOX (TIR1/AFB). CULLIN1-neddylation is required for SCFTIR1/AFBfunctionality, as exemplified by mutants deficient in the NEDD8-activating enzyme subunit AUXIN-RESISTANT 1 (AXR1). Here, we report a chemical biology screen that identifies small molecules requiring AXR1 to modulate plant development. We selected four molecules of interest, RubNeddin 1 to 4 (RN1 to -4), among which RN3 and RN4 trigger selective auxin responses at transcriptional, biochemical, and morphological levels. This selective activity is explained by their ability to consistently promote the interaction between TIR1 and a specific subset of AUX/IAA proteins, stimulating the degradation of particular AUX/IAA combinations. Finally, we performed a genetic screen using RN4, the RN with the greatest potential for dissecting auxin perception, which revealed that the chromatin remodeling ATPase BRAHMA is implicated in auxin-mediated apical hook development. These results demonstrate the power of selective auxin agonists to dissect auxin perception for plant developmental functions, as well as offering opportunities to discover new molecular players involved in auxin responses.

scholarly journals Light-induced primary amines and o-nitrobenzyl alcohols cyclization as a versatile photoclick reaction for modular conjugation

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
An-Di Guo ◽  
Dan Wei ◽  
Hui-Jun Nie ◽  
Hao Hu ◽  
Chengyuan Peng ◽  
...  
Keyword(s):  
Small Molecules ◽  
Click Chemistry ◽  
Chemical Biology ◽  
Materials Science ◽  
Primary Amines ◽  
Mild Conditions ◽  
Native Proteins ◽  
Good Biocompatibility ◽  
Operational Simplicity

Abstract The advent of click chemistry has had a profound impact on many fields and fueled a need for reliable reactions to expand the click chemistry toolkit. However, developing new systems to fulfill the click chemistry criteria remains highly desirable yet challenging. Here, we report the development of light-induced primary amines and o-nitrobenzyl alcohols cyclization (PANAC) as a photoclick reaction via primary amines as direct click handle, to rapid and modular functionalization of diverse small molecules and native biomolecules. With intrinsic advantages of temporal control, good biocompatibility, reliable chemoselectivity, excellent efficiency, readily accessible reactants, operational simplicity and mild conditions, the PANAC photoclick is robust for direct diversification of pharmaceuticals and biorelevant molecules, lysine-specific modifications of unprotected peptides and native proteins in vitro, temporal profiling of endogenous kinases and organelle-targeted labeling in living systems. This strategy provides a versatile platform for organic synthesis, bioconjugation, medicinal chemistry, chemical biology and materials science.

scholarly journals Publisher Correction: Structural and chemical biology of deacetylases for carbohydrates, proteins, small molecules and histones

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Marco Bürger ◽  
Joanne Chory
Keyword(s):  
Small Molecules ◽  
Chemical Biology ◽  
Xanthomonas Campestris ◽  
Geobacillus Stearothermophilus

In the original published version of the article, the protein name for the carbohydrate deacetylase in Geobacillus stearothermophilus was missing from Table 1. The protein name, Axe2 (corresponding to PDB code 3W7V), should have appeared immediately following the species name. In addition, a space was inadvertently omitted between Xanthomonas campestris and ACDase in Table 1. The errors have been corrected in the HTML and PDF versions.

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