Related Experiment Video
Updated: Aug 22, 2025
08:47
Synthesis and Bioconjugation of Thiol-Reactive Reagents for the Creation of Site-Selectively Modified Immunoconjugates
Published on: March 6, 2019
9.5K
Thiol-Michael addition based conjugate for glutathione activation and release
Zhengkun Liu1, Shasha Chen1, Hao Wang1
1Department of Animal and Biomedical Sciences, School of Life Sciences, Lanzhou University, 222 Tianshui South Road, Lanzhou 730000, China.
Bioorganic Chemistry
|November 7, 2022
Summary
Researchers developed TC6, a new glutathione-responsive drug delivery system. This conjugate enhances anti-tumor efficacy by targeting cancer cells, offering a promising approach for drug development.
Area of Science:
- Bioconjugation Chemistry
- Cancer Therapeutics
- Biomarker Development
Background:
- Glutathione (GSH) is a critical tumor biomarker.
- Existing GSH-mediated drug systems primarily use disulfide conjugates.
- Novel GSH-responsive systems are needed for improved cancer diagnosis and treatment.
Purpose of the Study:
- To introduce a novel thiol-Michael addition-based GSH-responsive conjugate, TC6.
- To evaluate TC6's synthesis, selectivity, and stability for glutathione.
- To assess the anti-tumor efficacy of camptothecin delivered by TC6.
Main Methods:
- Synthesis of the tricyclic TC6 conjugate featuring α, β-unsaturated ketone moieties.
- In vitro assessment of TC6 selectivity and stability towards glutathione.
- In vitro and in vivo evaluation of camptothecin delivery using TC6 in cancer models.
Main Results:
- TC6 was easily synthesized with good selectivity and stability for glutathione.
- Camptothecin delivery via TC6 demonstrated enhanced anti-tumor activity in cellular and animal models.
- The conjugate showed potential for targeted drug delivery in cancer therapy.
Conclusions:
- TC6 represents a novel GSH-responsive platform utilizing thiol-Michael addition.
- This conjugate system offers improved anti-tumor efficacy compared to conventional methods.
- TC6 holds promise for developing advanced antibody or small molecule-conjugated anti-cancer drugs.
More Related Videos
Related Concept Videos
01:22Phase II Reactions: Glutathione Conjugation and Mercapturic Acid Formation
317
Glutathione, a tripeptide made up of glutamate, cysteine, and glycine, is a critical player in the detoxification of drugs and xenobiotics via a process known as glutathione conjugation or mercapturic acid formation. This phase II biotransformation reaction involves the covalent binding of glutathione to a drug or its metabolite, enhancing the compound's water solubility and enabling its excretion.
Several distinctive characteristics distinguish glutathione conjugation from other phase II...
Several distinctive characteristics distinguish glutathione conjugation from other phase II...
317
02:33Preparation and Reactions of Thiols
6.6K
Thiols are prepared using the hydrosulfide anion as a nucleophile in a nucleophilic substitution reaction with alkyl halides. For instance, bromobutane reacts with sodium hydrosulfide to give butanethiol.
6.6K
01:08Conjugate Addition of Enolates: Michael Addition
2.8K
The attack of a nucleophile at the β carbon of an α,β-unsaturated carbonyl compound is called conjugate addition. Conjugate addition reactions of active methylene compounds, such as β-diketones, β-keto esters, β-keto nitriles, and α-nitro ketones, are called Michael addition reactions.
2.8K
01:19Phase II Reactions: Sulfation and Conjugation with α-Amino Acids
346
Sulfation and α-amino acid conjugation are two critical biotransformation reactions in drug metabolism. Sulfation, a phase II biotransformation reaction, involves adding a polar sulfate group to a drug, enhancing its water solubility and promoting excretion. This process can either co-occur with or occur independently of glucuronidation. Nonmicrosomal sulfotransferase enzymes catalyze the process. The reaction involves 3'-phosphoadenosine-5'-phosphosulfate or PAPS coenzyme...
346
01:14Drug Metabolism: Phase II Reactions
4.0K
Phase II reactions are essential for the detoxification and elimination of drugs from the body. These reactions involve the conjugation of parent drugs or their phase I metabolites with endogenous molecules, resulting in more hydrophilic drug conjugates. The primary conjugation reactions in this phase are sulfation and glucuronidation. Both sulfation and glucuronidation typically produce biologically inactive metabolites. However, in some cases involving prodrugs, active metabolites may be...
4.0K
01:24Phase II Reactions: Glucuronidation
656
Glucuronidation, a pivotal phase II biotransformation process, involves the coupling of glucuronic acid to a drug or xenobiotic. Given its widespread occurrence and critical role in drug metabolism, it's considered the most crucial phase II reaction. It enhances the water solubility of substances, aiding their expulsion from the body. The driving force behind these reactions is a group of enzymes known as UDP-glucuronosyltransferases (UGTs). UGTs facilitate the transfer of a glucuronic acid...
656