How Do Microbial Metabolites Interact with Their Protein Targets? DOI

Mario Astigarraga,

Andrés Sánchez-Ruiz,

Aminata Diop-Aw

et al.

Journal of Chemical Information and Modeling, Journal Year: 2025, Volume and Issue: 65(1), P. 201 - 213

Published: Jan. 2, 2025

The design of drugs and nutraceutics that mimic microbial metabolites is an emerging drug modality in medicinal chemistry attempts to modulate the myriad interactions these molecules establish with host proteins. Understanding how interact their target proteins key perform a rational metabolite mimetic for therapeutic usage. In present work, we address this question by analyzing functional groups they display set more than 71K protein–metabolite from PDB. Significant differences group distributions, chemical features, co-occurrences are observed distinct subsets molecules. same true distributions interaction types. By correlating both data sets, able explain patterns terms patterns. These results will shed light on novel purposes.

Language: Английский

Chlorinated Solvents: Their Advantages, Disadvantages, and Alternatives in Organic and Medicinal Chemistry DOI
Andrew Jordan,

Patrick Stoy,

Helen F. Sneddon

et al.

Chemical Reviews, Journal Year: 2020, Volume and Issue: 121(3), P. 1582 - 1622

Published: Dec. 22, 2020

Chlorinated solvents were once, and in many places are still, ubiquitous chemistry laboratories. This review explores the properties that led to such widespread use, why there is now an increasing drive minimize usage, what alternatives currently available.

Language: Английский

Citations

108
The role of reversible and irreversible covalent chemistry in targeted protein degradation DOI Creative Commons
Hannah Kiely‐Collins, Georg E. Winter, Gonçalo J. L. Bernardes

et al.

Cell chemical biology, Journal Year: 2021, Volume and Issue: 28(7), P. 952 - 968

Published: March 30, 2021

Language: Английский

Citations

91
A solvent-reagent selection guide for Steglich-type esterification of carboxylic acids DOI Creative Commons
Andrew Jordan,

Kyran D. Whymark,

Jack D. Sydenham

et al.

Green Chemistry, Journal Year: 2021, Volume and Issue: 23(17), P. 6405 - 6413

Published: Jan. 1, 2021

A solvent-reagent selection guide for Steglich esterification has been developed. Safer, more sustainable combinations were identified and optimized this transformation effectively replacing the harmful, toxic status quo .

Language: Английский

Citations

73
Deep generative design with 3D pharmacophoric constraints DOI Creative Commons
Fergus Imrie, Thomas E. Hadfield, A.R. Bradley

et al.

Chemical Science, Journal Year: 2021, Volume and Issue: 12(43), P. 14577 - 14589

Published: Jan. 1, 2021

A novel deep generative model combines convolution and graph neural networks to allow 3D-aware molecular design. We show how 3D pharmacophoric information can be incorporated into models apply our both linker R-group

Language: Английский

Citations

69
The Time and Place for Nature in Drug Discovery DOI Creative Commons
Robert J. Young, Sabine L. Flitsch, Michael Grigalunas

et al.

JACS Au, Journal Year: 2022, Volume and Issue: 2(11), P. 2400 - 2416

Published: Oct. 14, 2022

The case for a renewed focus on Nature in drug discovery is reviewed; not terms of natural product screening, but how and why biomimetic molecules, especially those produced by processes, should deliver the age artificial intelligence screening vast collections both vitro silico. declining product-likeness licensed drugs consequent physicochemical implications this trend context current practices are noted. To arrest these trends, logic seeking new bioactive agents with enhanced mimicry considered; notably that molecules constructed proteins (enzymes) more likely to interact other (e.g., targets transporters), notion validated products. Nature's finite number building blocks their interactions necessarily reduce potential numbers structures, yet enable expansion chemical space inherent diversity physical characteristics, pertinent property-based design. feasible variations motifs considered expanded encompass pseudo-natural products, leading further logical step harnessing bioprocessing routes access them. Together, offer opportunities enhancing mimicry, thereby bringing innovation synthesis exploiting characteristics recognition processes. computational guidance help identifying binding commonalities route map opportunity design tailored "organic/biological" rather than purely "synthetic" structures. prototype structures pay dividends disposition efficacy while inherently enabling greener sustainable manufacturing techniques.

Language: Английский

Citations

67
The Chosen Few: Parallel Library Reaction Methodologies for Drug Discovery DOI

Amanda W. Dombrowski,

Ana L. Aguirre,

Anurupa Shrestha

et al.

The Journal of Organic Chemistry, Journal Year: 2021, Volume and Issue: 87(4), P. 1880 - 1897

Published: Nov. 15, 2021

Parallel library synthesis is an important tool for drug discovery because it enables the of closely related analogues in parallel via robust and general synthetic transformations. In this perspective, we analyzed methodologies used >5000 libraries representing 15 prevalent The data set contains complex substrates diverse arrays building blocks over last 14 years at AbbVie. that have demonstrated robustness generality with proven success are described along their substrate scopes. evolution past decade discussed. We also highlight combination high-throughput experimentation will continue to facilitate library-amenable discovery.

Language: Английский

Citations

65
Amino-oxetanes as amide isosteres by an alternative defluorosulfonylative coupling of sulfonyl fluorides DOI
Juan J. Rojas, Rosemary A. Croft, Alistair J. Sterling

et al.

Nature Chemistry, Journal Year: 2022, Volume and Issue: 14(2), P. 160 - 169

Published: Jan. 27, 2022

Language: Английский

Citations

55
Trends in small molecule drug properties: A developability molecule assessment perspective DOI

Prashant Agarwal,

James E. Huckle,

Jake Newman

et al.

Drug Discovery Today, Journal Year: 2022, Volume and Issue: 27(12), P. 103366 - 103366

Published: Sept. 17, 2022

Language: Английский

Citations

51
Photoactivation of Boronic Acid Prodrugs via a Phenyl Radical Mechanism: Iridium(III) Anticancer Complex as an Example DOI

Moyi Liu,

Yunli Luo,

Junyu Yan

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(18), P. 10082 - 10091

Published: April 26, 2023

Boronic acid (or ester) is a well-known temporary masking group for developing anticancer prodrugs responsive to tumoral reactive oxygen species (ROS), but their clinic application largely hampered by the low activation efficiency. Herein, we report robust photoactivation approach that can spatiotemporally convert boronic acid-caged iridium(III) complex IrBA into bioactive IrNH2 under hypoxic tumor microenvironments. Mechanistic studies show phenyl moiety in equilibrium with boronate anion be photo-oxidized generate radical, highly capable of rapidly capturing O2 at extremely concentrations (down 0.02%). As result, while could hardly activated intrinsic ROS cancer cells, upon light irradiation, prodrug efficiently converted even limited supply, along direct damage mitochondrial DNA and potent antitumor activities 2D monolayer 3D spheroids, mice bearing xenografts. Of note, extended intermolecular photocatalytic external photosensitizers red absorption activate compounds, thus offering general organoboron prodrugs.

Language: Английский

Citations

38
Chitosan-Based Hydrogel in the Management of Dermal Infections: A Review DOI Creative Commons
Popat Mohite,

Pudji Rahayu,

Shubham Munde

et al.

Gels, Journal Year: 2023, Volume and Issue: 9(7), P. 594 - 594

Published: July 24, 2023

The main objective of this review is to provide a comprehensive overview the current evidence regarding use chitosan-based hydrogels manage skin infections. Chitosan, naturally occurring polysaccharide derived from chitin, possesses inherent antimicrobial properties, making it promising candidate for treating various dermal This follows systematic approach analyze relevant studies that have investigated effectiveness in context By examining available evidence, aims evaluate these hydrogels' overall efficacy, safety, and potential applications managing review's primary focus gather data different recent about combating infections; includes assessing their ability inhibit growth microorganisms reduce infection-related symptoms. Furthermore, also considers safety profile hydrogels, any adverse effects associated with use. evaluation crucial ensure can be safely utilized management infections without causing harm patients. healthcare professionals researchers understanding infection management. findings contribute informed decision-making development treatment strategies field.

Language: Английский

Citations

35