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Related Concept Videos

Inhibitors of Bacterial Protein Synthesis01:25

Inhibitors of Bacterial Protein Synthesis

Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S...
Types of RNA01:23

Types of RNA

Overview
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
Inhibitors of Bacterial DNA Synthesis01:28

Inhibitors of Bacterial DNA Synthesis

Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These antibiotics are selectively...
Ribosomal RNA Synthesis02:53

Ribosomal RNA Synthesis

Ribosome synthesis is a highly complex and coordinated process involving more than 200 assembly factors. The synthesis and processing of ribosomal components occurs not only in the nucleolus but also in the nucleoplasm and the cytoplasm of eukaryotic cells.
Ribosome biogenesis begins with the synthesis of 5S and 45S pre-rRNAs by distinct RNA polymerases. The primary transcripts are extensively processed and modified before they are bound and folded by ribosomal proteins and assembly factors,...
Ribosomal RNA Synthesis02:53

Ribosomal RNA Synthesis

Ribosome synthesis is a highly complex and coordinated process involving more than 200 assembly factors. The synthesis and processing of ribosomal components occurs not only in the nucleolus but also in the nucleoplasm and the cytoplasm of eukaryotic cells.
Ribosome biogenesis begins with the synthesis of 5S and 45S pre-rRNAs by distinct RNA polymerases. The primary transcripts are extensively processed and modified before they are bound and folded by ribosomal proteins and assembly factors,...
Riboswitches01:56

Riboswitches

Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...

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RIBO-seq in Bacteria: a Sample Collection and Library Preparation Protocol for NGS Sequencing
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Published on: August 7, 2021

Designed spiro-bicyclic analogues targeting the ribosomal decoding center.

Thomas Cottin1, Constantina Pyrkotis, Christos I Stathakis

  • 1Laboratory of Chemical Biology of Natural Products and Designed Molecules, Institute of Physical Chemistry, N.C.S.R. "Demokritos", 15310 Ag. Paraskevi Attikis, Athens, Greece.

Chembiochem : a European Journal of Chemical Biology
|December 15, 2010
PubMed
Summary

Researchers designed novel spirocyclic scaffolds that mimic natural antibiotics targeting bacterial ribosomes. These compounds show potential for inhibiting bacterial protein synthesis and developing new antibiotic therapies.

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Area of Science:

  • Medicinal Chemistry
  • Molecular Biology
  • Drug Discovery

Background:

  • Bacterial ribosomes are key targets for antibiotics inhibiting protein synthesis.
  • Aminoglycosides are crucial for RNA recognition and serve as templates for novel RNA binders.
  • Existing RNA-targeting molecule designs often focus on modifying aminoglycosidic structures.

Purpose of the Study:

  • To design and synthesize rigid spirocyclic scaffolds with a predicted ribosome-bound conformation.
  • To evaluate the binding affinities of these novel analogues to the ribosomal A-site.
  • To assess the potential of these compounds in inhibiting bacterial protein production.

Main Methods:

  • Rational design of rigid spirocyclic scaffolds.
  • Chemical synthesis of novel analogues.
  • Assessment of binding affinities to the ribosomal A-site.
  • In vitro evaluation of protein synthesis inhibition.

Main Results:

  • Successfully designed and synthesized rigid spirocyclic scaffolds.
  • Analogues mimic interactions of natural products with the ribosomal A-site, confirmed by binding affinities.
  • Optimized synthesis approach developed.
  • Demonstrated potential to inhibit bacterial protein production in vitro.

Conclusions:

  • Novel spirocyclic scaffolds effectively mimic natural antibiotic interactions with bacterial ribosomes.
  • The developed compounds show promise for inhibiting bacterial protein synthesis.
  • These findings provide a foundation for developing new antibiotics with improved profiles.