Please use this identifier to cite or link to this item: https://doi.org/10.1002/cmdc.201500414
Title: Optimization of Inhibitors of Mycobacterium tuberculosis Pantothenate Synthetase Based on Group Efficiency Analysis
Authors: Hung, A.W 
Silvestre, H.L
Wen, S
George, G.P.C
Boland, J
Blundell, T.L
Ciulli, A
Abell, C
Keywords: antimycobacterial agent
bacterial enzyme
enzyme inhibitor
functional group
pantothenate synthetase
pantothenate synthetase inhibitor
unclassified drug
enzyme inhibitor
pantothenate synthetase
peptide synthase
tuberculostatic agent
Article
binding affinity
crystal structure
drug binding site
drug design
drug potency
drug protein binding
drug screening
drug structure
fragment based screening
group efficiency analysis
isothermal titration calorimetry
ligand binding
Mycobacterium tuberculosis
nonhuman
priority journal
substitution reaction
X ray crystallography
antagonists and inhibitors
chemical structure
chemistry
dose response
drug development
enzymology
metabolism
molecular model
Mycobacterium tuberculosis
procedures
structure activity relation
synthesis
Antitubercular Agents
Crystallography, X-Ray
Dose-Response Relationship, Drug
Drug Discovery
Enzyme Inhibitors
Models, Molecular
Molecular Structure
Mycobacterium tuberculosis
Peptide Synthases
Structure-Activity Relationship
Issue Date: 2016
Citation: Hung, A.W, Silvestre, H.L, Wen, S, George, G.P.C, Boland, J, Blundell, T.L, Ciulli, A, Abell, C (2016). Optimization of Inhibitors of Mycobacterium tuberculosis Pantothenate Synthetase Based on Group Efficiency Analysis. ChemMedChem 11 (1) : 38-42. ScholarBank@NUS Repository. https://doi.org/10.1002/cmdc.201500414
Rights: Attribution 4.0 International
Abstract: Ligand efficiency has proven to be a valuable concept for optimization of leads in the early stages of drug design. Taking this one step further, group efficiency (GE) evaluates the binding efficiency of each appendage of a molecule, further fine-tuning the drug design process. Here, GE analysis is used to systematically improve the potency of inhibitors of Mycobacterium tuberculosis pantothenate synthetase, an important target in tuberculosis therapy. Binding efficiencies were found to be distributed unevenly within a lead molecule derived using a fragment-based approach. Substitution of the less efficient parts of the molecule allowed systematic development of more potent compounds. This method of dissecting and analyzing different groups within a molecule offers a rational and general way of carrying out lead optimization, with potential broad application within drug discovery. © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
Source Title: ChemMedChem
URI: https://scholarbank.nus.edu.sg/handle/10635/179944
ISSN: 18607179
DOI: 10.1002/cmdc.201500414
Rights: Attribution 4.0 International
Appears in Collections:Staff Publications
Elements

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1002_cmdc_201500414.pdf2.08 MBAdobe PDF

OPEN

NoneView/Download

SCOPUSTM   
Citations

19
checked on Apr 4, 2021

Page view(s)

37
checked on Apr 8, 2021

Google ScholarTM

Check

Altmetric


This item is licensed under a Creative Commons License Creative Commons