Related Experiment Video
Updated: Mar 6, 2026
13:49
Semi-automated Biopanning of Bacterial Display Libraries for Peptide Affinity Reagent Discovery and Analysis of Resulting Isolates
Published on: December 6, 2017
12.1K
Structure-based discovery of LpxC inhibitors
Jing Zhang1, Audrey Chan1, Blaise Lippa1
1Cubist Pharmaceuticals Inc., 65 Hayden Avenue, Lexington, MA 02421, USA.
Bioorganic & Medicinal Chemistry Letters
|March 18, 2017
Summary
Multidrug-resistant Gram-negative bacteria threaten public health. This study presents novel inhibitors targeting UDP-3-O-(R-3-hydroxymyristol)-N-acetylglucosamine deacetylase (LpxC), an essential enzyme for bacterial survival.
Area of Science:
- Microbiology
- Medicinal Chemistry
- Drug Discovery
Background:
- Multidrug-resistant (MDR) Gram-negative bacteria pose a significant global health risk.
- Urgent need for novel antimicrobial agents to combat resistance.
- Lipid A biosynthesis is crucial for Gram-negative bacterial survival.
Purpose of the Study:
- To discover novel inhibitors of UDP-3-O-(R-3-hydroxymyristol)-N-acetylglucosamine deacetylase (LpxC).
- To identify potential therapeutic agents against MDR Gram-negative bacteria.
Main Methods:
- Enzyme inhibition assays targeting LpxC.
- Structure-based drug design approaches.
- Chemical synthesis of potential LpxC inhibitors.
Main Results:
- Identification of novel chemical scaffolds with LpxC inhibitory activity.
- Characterization of the mechanism of inhibition.
- Preliminary assessment of antibacterial efficacy.
Conclusions:
- LpxC is a promising target for developing new antibiotics against Gram-negative pathogens.
- The identified inhibitors represent a starting point for further drug development.
- Targeting lipid A biosynthesis offers a viable strategy to overcome MDR infections.
Related Concept Videos
01:26Drug Discovery: Overview
12.5K
Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
12.5K
02:04Protein-protein Interfaces
14.9K
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...
14.9K
02:40Ligand Binding Sites
15.5K
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
15.5K