Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Inhibitors of Gram-positive Cell Wall Synthesis

Inhibitors of Gram-positive Cell Wall Synthesis

Bacterial cell walls are typically rigid structures composed mainly of peptidoglycan, a mesh-like polymer that provides mechanical strength and maintains cell shape. The synthesis of peptidoglycan is a crucial process in bacterial growth and serves as a primary target for many antibiotics.Mechanism of Action of Beta-Lactam AntibioticsBeta-lactam antibiotics, such as penicillin, inhibit peptidoglycan synthesis in actively growing cells. These antibiotics share a characteristic four-membered...

Inhibitors of Bacterial Protein Synthesis

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...

Inhibitors of Bacterial DNA Synthesis

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...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

Myostatin Inhibitory D‑Peptides Induce Skeletal Muscle Hypertrophy along with Alteration of Bioactive Sphingolipid Metabolism.

ACS pharmacology & translational science·2026

Same author

Non-amputative wide local excision with partial bone resection for subungual melanoma involving the distal phalanx.

Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG·2026

Same author

Development of Novel Lysosome-Targeting Chimera by Non-covalent-Type Fc-IGF2 Complex (Fc-LYTAC) for Target Membrane Protein Degradation.

Chemical & pharmaceutical bulletin·2026

Same author

Intranasal Administration of a Neuromedin-U Receptor 2-Specific Peptide Agonist for Obesity Treatment: Effect of the Stability on Brain Delivery.

Molecular pharmaceutics·2026

Same author

A Cysteine-Dependent Peptide Cyclase with Broad Substrate Tolerance Enables Chemoenzymatic Synthesis of Macolacin Analogs.

ACS chemical biology·2026

Same author

Molecular functions and applications of peptide agonists acting on mouse neuromedin U receptor 1.

Bioorganic & medicinal chemistry·2026

Search research articles

Related Experiment Video

Updated: Jun 4, 2026

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

Development of Conformationally Restricted Negamycin Derivatives for Potent Readthrough Activity.

Noriko Omura¹, Akihiro Taguchi¹, Tomoki Kuwahara²

¹Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.

ACS Medicinal Chemistry Letters

|December 20, 2023

Summary

New negamycin derivatives, TCP-304 and TCP-306, show potent readthrough activity for Duchenne muscular dystrophy (DMD) mutations. These conformationally restricted compounds restore dystrophin, offering a promising therapeutic avenue for DMD.

More Related Videos

Antimicrobial Peptides Produced by Selective Pressure Incorporation of Non-canonical Amino Acids

Antimicrobial Peptides Produced by Selective Pressure Incorporation of Non-canonical Amino Acids

Published on: May 4, 2018

Visualization of Bacterial Resistance using Fluorescent Antibiotic Probes

Visualization of Bacterial Resistance using Fluorescent Antibiotic Probes

Published on: March 2, 2020

Related Experiment Videos

Last Updated: Jun 4, 2026

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

Antimicrobial Peptides Produced by Selective Pressure Incorporation of Non-canonical Amino Acids

Antimicrobial Peptides Produced by Selective Pressure Incorporation of Non-canonical Amino Acids

Published on: May 4, 2018

Visualization of Bacterial Resistance using Fluorescent Antibiotic Probes

Visualization of Bacterial Resistance using Fluorescent Antibiotic Probes

Published on: March 2, 2020

Area of Science:

Medicinal Chemistry
Molecular Biology
Genetics

Background:

Duchenne muscular dystrophy (DMD) is a genetic disorder caused by mutations in the dystrophin gene.
(+)-Negamycin and its analogue TCP-107 exhibit readthrough activity, restoring dystrophin.
Previous studies indicated TCP-107 has higher readthrough activity than negamycin.

Purpose of the Study:

To design and synthesize novel cyclopropane-based, conformationally restricted derivatives of TCP-107.
To evaluate the readthrough activity of these derivatives in a cell-based reporter assay for DMD-associated mutations.
To identify derivatives with enhanced therapeutic potential for Duchenne muscular dystrophy.

Main Methods:

Synthesis of cyclopropane-based conformationally restricted derivatives of TCP-107.
Evaluation of readthrough activity using a cell-based reporter assay against TGA-type mutations.
Structure-activity relationship analysis of synthesized compounds.

Main Results:

A down-cis isomer, TCP-304, demonstrated significant readthrough activity.
TCP-306, a derivative acylated with l-α-aminoundecanoic acid, showed approximately three times higher activity than TCP-304.
These derivatives exhibited dose-dependent activity and were effective against both TGA and TAG mutations.

Conclusions:

Conformational restriction of negamycin derivatives via cyclopropane ring introduction enhances potent readthrough activity.
TCP-304 and TCP-306 represent promising candidates for Duchenne muscular dystrophy therapeutic development.
The findings suggest a viable strategy for developing novel readthrough compounds for genetic disorders.