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
-
Targeting Inhibition of COX-2: A Review of Patents, 2002 - 2006
Recent Patents on Inflammation & Allergy Drug Discovery Anti-inflammatory Effect of Predimenol, A Bioactive Extract from <i>Phaleria macrocarpa</i>, through the Suppression of NF-κB and COX-2
Recent Advances in Inflammation & Allergy Drug Discovery Self-Assembly of DNA and Cell-Adhesive Proteins onto pH-Sensitive Inorganic Crystals for Precise and Efficient Transgene Delivery
Current Pharmaceutical Design The Use of Ligands in Copper-Catalyzed [3+2] Azide-Alkyne Cycloaddition: Clicker than Click Chemistry?
Current Organic Chemistry ATF4, DLX3, FRA1, MSX2, C/EBP-ζ, and C/EBP-α Shape the Molecular Basis of Therapeutic Effects of Zoledronic Acid in Bone Disorders
Anti-Cancer Agents in Medicinal Chemistry Neuropeptidomics: Improvements in Mass Spectrometry Imaging Analysis and Recent Advancements
Current Protein & Peptide Science A Sialic Acid-Specific Lectin from the Mushroom Paecilomyces Japonica that Exhibits Hemagglutination Activity and Cytotoxicity
Protein & Peptide Letters Computational Methods and Algorithms for Mass-Spectrometry Based Differential Proteomics
Current Proteomics Type I Collagen and Collagen Mimetics as Angiogenesis Promoting Superpolymers
Current Pharmaceutical Design Synthesis, Biological and Computational Evaluation of Novel Oxindole Derivatives as Inhibitors of Src Family Kinases
Letters in Drug Design & Discovery Core Functional Sequence of C-terminal GAG-binding Domain Directs Cellular Uptake of IGFBP-3-derived Peptides
Protein & Peptide Letters Folic Acid Conjugated Chitosan Nanoparticles for Tumor Targeting of Therapeutic and Imaging Agents
Pharmaceutical Nanotechnology Ceftriaxone-Vancomycin Drug Toxicity Reduction by VRP 1020 in Mus musculus Mice
Current Clinical Pharmacology Personalization of Targeted Therapy in Advanced Thyroid Cancer
Current Genomics Molecular and Thermodynamic Studies on DNA Triplex Formed in the Promoter Region of HMGB1 Gene as a Selective Target for Anticancer Drugs
Anti-Cancer Agents in Medicinal Chemistry Therapeutic Monoclonal Antibodies: Strategies and Challenges for Biosimilars Development
Current Medicinal Chemistry Production of Non Viral DNA Vectors
Current Gene Therapy Bioinformatic Analysis Reveals Key Genes and Pathways in Aging Brain of Senescence-accelerated Mouse P8 (SAMP8)
CNS & Neurological Disorders - Drug Targets Processing and Regulation Mechanisms within Antigen Presenting Cells: A Possibility for Therapeutic Modulation
Current Pharmaceutical Design Antimicrobial and Antioxidant Properties of <i>Satureja Montana</i> L. and S. Subspicata Vis. (Lamiaceae)
Current Drug Targets