Abstract
New antibacterial drugs are urgently needed to combat the growing problem of multidrug resistant bacterial infections. Major advances in bacterial genomics have uncovered many unexploited targets, leading to the possibility of discovering new antibacterials with novel mechanisms that would circumvent resistance. Many of these targets are soluble enzymes that vary in their degrees of mechanistic complexity. Protein crystallography as well as solution based biophysical methods are playing an increasingly important role in selecting, characterizing and validating promising targets as well as identifying and optimizing lead compounds that inhibit their functions. Advances made in recent years in sensitivity, resolution and throughput of biophysical tools are allowing multiple approaches to screening for hits and rational design of leads based on a deeper understanding of structure-activity relationships. However, the path from a lead compound to a safe and efficacious antibacterial drug still remains challenging. Structural and biophysical approaches have had less of an impact on this later phase of discovery than on the lead generation phase.
Keywords: Antibacterial drugs, bacterial targets, biophysical tools, lead generation, target validation, crystal structure, NMR spectroscopy, biophysical approaches, screening, KdsA
Current Drug Targets
Title: Applications of Biophysical Tools to Target-Based Discovery of Novel Antibacterial Leads
Volume: 13 Issue: 3
Author(s): Sushmita Lahiri, Steven Kazmirski, Gunther Kern and Gautam Sanyal
Affiliation:
Keywords: Antibacterial drugs, bacterial targets, biophysical tools, lead generation, target validation, crystal structure, NMR spectroscopy, biophysical approaches, screening, KdsA
Abstract: New antibacterial drugs are urgently needed to combat the growing problem of multidrug resistant bacterial infections. Major advances in bacterial genomics have uncovered many unexploited targets, leading to the possibility of discovering new antibacterials with novel mechanisms that would circumvent resistance. Many of these targets are soluble enzymes that vary in their degrees of mechanistic complexity. Protein crystallography as well as solution based biophysical methods are playing an increasingly important role in selecting, characterizing and validating promising targets as well as identifying and optimizing lead compounds that inhibit their functions. Advances made in recent years in sensitivity, resolution and throughput of biophysical tools are allowing multiple approaches to screening for hits and rational design of leads based on a deeper understanding of structure-activity relationships. However, the path from a lead compound to a safe and efficacious antibacterial drug still remains challenging. Structural and biophysical approaches have had less of an impact on this later phase of discovery than on the lead generation phase.
Export Options
About this article
Cite this article as:
Lahiri Sushmita, Kazmirski Steven, Kern Gunther and Sanyal Gautam, Applications of Biophysical Tools to Target-Based Discovery of Novel Antibacterial Leads, Current Drug Targets 2012; 13 (3) . https://dx.doi.org/10.2174/138945012799424660
DOI https://dx.doi.org/10.2174/138945012799424660 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...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
Related Articles
-
Atmospheric Concentrations of Polycyclic Aromatic Hydrocarbons (PAHs) in India and South Korea: A Review
Mini-Reviews in Organic Chemistry Hypericin - The Facts About a Controversial Agent
Current Pharmaceutical Design Tricyclic Antidepressants-loaded Biodegradable PLGA Nanoparticles: In Vitro Characterization and In Vivo Analgesic and Anti-Allodynic Effect
Current Nanoscience Role of Infrared Spectroscopy and Imaging in Cancer Diagnosis
Current Medicinal Chemistry Biodegradable Composite Scaffolds: A Strategy to Modulate Stem Cell Behaviour
Recent Patents on Drug Delivery & Formulation An Overview of Galenic Preparation Methods for Medicinal Cannabis
Current Bioactive Compounds Rational Drug Design Paradigms: The Odyssey for Designing Better Drugs
Combinatorial Chemistry & High Throughput Screening The Leptin System: A Potential Target for Sepsis Induced Immune Suppression
Endocrine, Metabolic & Immune Disorders - Drug Targets A Convenient Synthesis of New 2-Cyanomethylthieno[3,2-e][1,2,4]- triazolo[1,5-c]pyrimidine Derivatives
Letters in Organic Chemistry Phytochemical Screening and Antibacterial Activity of Aloe Vera Collected from Different Climatic Regions of India
The Natural Products Journal Synthesis of Metabolites of Polycyclic Aromatic Hydrocarbons
Mini-Reviews in Organic Chemistry The Microbial Quality Aspects and Decontamination Approaches for the Herbal Medicinal Plants and Products: An in-Depth Review
Current Pharmaceutical Design Effectiveness of Resveratrol Against Cardiovascular Disease
Mini-Reviews in Organic Chemistry Nanocapsulated Ascorbic Acid in Combating Cerebral Ischemia Reperfusion- Induced Oxidative Injury in Rat Brain
Current Alzheimer Research Stimuli-induced Pulsatile or Triggered Release Delivery Systems for Bioactive Compounds
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Preparation of Knockout Extract for Determination of Really Active Compound Using MAb
Current Drug Discovery Technologies A Phenotypic Screen for Small-Molecule Inhibitors of Constitutively Active Mutant Thrombopoietin Receptor Implicated in Myeloproliferative Neoplasms
Combinatorial Chemistry & High Throughput Screening Modulating Poly (ADP-Ribose) Polymerase Activity: Potential for the Prevention and Therapy of Pathogenic Situations Involving DNA Damage and Oxidative Stress
Current Pharmaceutical Biotechnology Curcumin-based Nanoformulations to Target Breast Cancer: Current Trends and Challenges
Current Nanomaterials Activity Based Probes for Proteases: Applications to Biomarker Discovery,Molecular Imaging and Drug Screening
Current Pharmaceutical Design