Abstract
The history of fragment-based drug discovery, with an emphasis on crystallographic methods, is sketched, illuminating various contributions, including our own, which preceded the industrial development of the method. Subsequently, the creation of the BMSC fragment cocktails library is described. The BMSC collection currently comprises 68 cocktails of 10 compounds that are shape-wise diverse. The utility of these cocktails for initiating lead discovery in structure-based drug design has been explored by soaking numerous protein crystals obtained by our MSGPP (Medical Structural Genomics of Pathogenic Protozoa) consortium. Details of the fragment selection and cocktail design procedures, as well as examples of the successes obtained are given. The BMSC Fragment Cocktail recipes are available free of charge and are in use in over 20 academic labs.
Keywords: Structural genomics, drug design, malaria, trypanosomiasis, leishmaniasis, history
Current Topics in Medicinal Chemistry
Title: Fragment-Based Cocktail Crystallography by the Medical Structural Genomics of Pathogenic Protozoa Consortium
Volume: 9 Issue: 18
Author(s): Jonathan M. Caruthers, Wim G.J. Hol, Ethan A. Merritt, Frederick S. Buckner, Wesley C. Van Voorhis, Frank Zucker, Natasha Mueller, Angela Kelley, Alberto Napuli, Isolde LeTrong, Eric T. Larson, Christophe L.M.J. Verlinde, Jurgen Bosch, Tracy L. Arakaki, Liren Xiao, Jessica Kim, Jennifer Ross, Wei Deng, Zhihua Sun, Zhongsheng Zhang, Sayaka Shibata and Erkang Fan
Affiliation:
Keywords: Structural genomics, drug design, malaria, trypanosomiasis, leishmaniasis, history
Abstract: The history of fragment-based drug discovery, with an emphasis on crystallographic methods, is sketched, illuminating various contributions, including our own, which preceded the industrial development of the method. Subsequently, the creation of the BMSC fragment cocktails library is described. The BMSC collection currently comprises 68 cocktails of 10 compounds that are shape-wise diverse. The utility of these cocktails for initiating lead discovery in structure-based drug design has been explored by soaking numerous protein crystals obtained by our MSGPP (Medical Structural Genomics of Pathogenic Protozoa) consortium. Details of the fragment selection and cocktail design procedures, as well as examples of the successes obtained are given. The BMSC Fragment Cocktail recipes are available free of charge and are in use in over 20 academic labs.
Export Options
About this article
Cite this article as:
Caruthers M. Jonathan, Hol G.J. Wim, Merritt A. Ethan, Buckner S. Frederick, Van Voorhis C. Wesley, Zucker Frank, Mueller Natasha, Kelley Angela, Napuli Alberto, LeTrong Isolde, Larson T. Eric, Verlinde L.M.J. Christophe, Bosch Jurgen, Arakaki L. Tracy, Xiao Liren, Kim Jessica, Ross Jennifer, Deng Wei, Sun Zhihua, Zhang Zhongsheng, Shibata Sayaka and Fan Erkang, Fragment-Based Cocktail Crystallography by the Medical Structural Genomics of Pathogenic Protozoa Consortium, Current Topics in Medicinal Chemistry 2009; 9 (18) . https://dx.doi.org/10.2174/156802609790102383
DOI https://dx.doi.org/10.2174/156802609790102383 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Capsid (CA) Protein as a Novel Drug Target: Recent Progress in the Research of HIV-1 CA Inhibitors
Mini-Reviews in Medicinal Chemistry Immunopathological Aspects of Mycoplasma pneumoniae Infection
Current Pediatric Reviews Therapeutic DNA Delivery to Skeletal Muscle
Current Genomics Mass Spectrometry in High Throughput Screening: A Case Study on Acetyl-Coenzyme A Carboxylase using RapidFire® – Mass Spectrometry (RF-MS)
Combinatorial Chemistry & High Throughput Screening Targeting the LKB1 Tumor Suppressor
Current Drug Targets Computational Methods for Remote Homolog Identification
Current Protein & Peptide Science Thiazole Containing Heterocycles with Antimalarial Activity
Current Drug Discovery Technologies Chemistry and Biology of Heparin Mimetics that Bind to Fibroblast Growth Factors
Mini-Reviews in Medicinal Chemistry Recent Advances in the Development of Antiviral Agents Using Computer-aided Structure Based Approaches
Current Pharmaceutical Design Synthesis and Evaluation of N-Benzyl-Acridinone Derivatives Induced Apoptosis in Human Liver Cancer Cell-Lines
Letters in Drug Design & Discovery COVID-19/Any Respiratory Pandemic- What a Radiology Resident Must Know and Report
Current Medical Imaging A Stress Repair Mechanism That Maintains Vertebrate Structure During Stress
Cardiovascular & Hematological Disorders-Drug Targets Constrictive Pericarditis Associated with Coronavirus Disease 2019 (COVID-19): A Case Report
Infectious Disorders - Drug Targets Glycyrrhizic Acid Derivatives as New Antiviral and Immune Modulating Agents
Current Bioactive Compounds QSAR as a Tool for the Development of Potent Antiproliferative Agents by Inhibition of Choline Kinase
Current Computer-Aided Drug Design Effects of Elicitors, Viticultural Factors, and Enological Practices on Resveratrol and Stilbenes in Grapevine and Wine
Mini-Reviews in Medicinal Chemistry Synthesis of Novel Laurenditerpenol Analogues and their Evaluation as HIF-1 Activation Inhibitors
Letters in Organic Chemistry Antimitotic Chalcones and Related Compounds as Inhibitors of Tubulin Assembly
Anti-Cancer Agents in Medicinal Chemistry Natural Product-Based Antibiotics: Synthesis and SAR-Studies.
Current Pharmaceutical Design Crosstalk among Jasmonate, Salicylate and Ethylene Signaling Pathways in Plant Disease and Immune Responses
Current Protein & Peptide Science