Related Experiment Video

Updated: Oct 2, 2026

Synthesizing Amino Acids Modified with Reactive Carbonyls in Silico to Assess Structural Effects Using Molecular Dynamics Simulations
05:57

Synthesizing Amino Acids Modified with Reactive Carbonyls in Silico to Assess Structural Effects Using Molecular Dynamics Simulations

Published on: April 26, 2024

Identification of alpha-dicarbonyl scavengers for cellular protection against carbonyl stress

Georg T Wondrak1, Daniel Cervantes-Laurean, Michael J Roberts

  • 1Department of Pharmacology and Toxicology, College of Pharmacy, Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA.

Biochemical Pharmacology
|February 21, 2002
PubMed

Insights

Researchers identified D-penicillamine as a potent carbonyl scavenger, protecting cells from damage caused by reactive carbonyl species (RCS). This discovery offers a new therapeutic strategy against carbonyl stress, a factor in aging and disease.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Medicinal Chemistry

Background:

  • Protein and DNA damage from reactive oxygen species (ROS) and reactive carbonyl species (RCS) contribute to aging.
  • While ROS and some RCS (like methylglyoxal) have counteracting systems, other RCS-induced carbonyl stress lacks direct antioxidant or scavenger defenses.
  • Existing carbonyl scavengers are limited, necessitating new methods for identifying effective compounds.

Purpose of the Study:

  • To develop a novel screening method for identifying carbonyl scavengers, independent of antioxidant activity.
  • To identify potent inhibitors of non-oxidative advanced glycation and carbonyl stress.
  • To evaluate the cytoprotective effects of identified scavengers against carbonyl-induced toxicity.

Main Methods:

  • Developed a rapid glycation screening assay independent of oxygen to specifically identify carbonyl scavengers.
  • Utilized a 96-well microtiter plate format for high-throughput screening.
  • Performed comparative kinetic analyses and structure elucidation of reaction products.

Main Results:

  • Identified 3,3-dimethyl-D-cysteine as a potent inhibitor of non-oxidative advanced glycation.
  • D-penicillamine demonstrated superior alpha-oxoaldehyde-scavenging activity compared to aminoguanidine.
  • D-penicillamine forms a 2-acylthiazolidine derivative with alpha-oxoaldehydes and protects human skin cells from glyoxal and methylglyoxal toxicity.

Conclusions:

  • The developed screening method effectively identifies potent carbonyl scavengers.
  • D-penicillamine is a highly effective alpha-oxoaldehyde scavenger with significant cytoprotective properties.
  • The alpha-amino-beta-mercapto-beta,beta-dimethyl-ethane pharmacophore shows promise for developing new therapeutic agents against carbonyl stress.

More Related Videos

Imaging Approaches to Assessments of Toxicological Oxidative Stress Using Genetically-encoded Fluorogenic Sensors09:33

Imaging Approaches to Assessments of Toxicological Oxidative Stress Using Genetically-encoded Fluorogenic Sensors

Published on: February 7, 2018

Related Concept Videos

Protecting Groups for Aldehydes and Ketones: Introduction01:23

Protecting Groups for Aldehydes and Ketones: Introduction

Protecting groups are compounds that can bind to a specific functional group in the presence of other functional groups to protect them from undesired chemical reactions. These compounds can selectively bind to particular functional groups and advance chemoselective reactions in polyfunctional systems (Figure 1). After the functional group has served its purpose, it is removed by reacting it with specific compounds.
Radical Autoxidation01:20

Radical Autoxidation

The oxidation of an organic compound in the presence of air or oxygen is called autoxidation. For example, cumene reacts with oxygen to form hydroperoxide. Autoxidation involves initiation, propagation, and termination steps. Many organic compounds are susceptible to autoxidation—especially ethers in the presence of oxygen, which form hydroperoxides. Even though this reaction is slow, old ether bottles contain small amounts of peroxide, which leads to laboratory explosions during ether...
Acetals and Thioacetals as Protecting Groups for Aldehydes and Ketones01:24

Acetals and Thioacetals as Protecting Groups for Aldehydes and Ketones

Acetals are formed by reacting two equivalents of alcohol with carbonyl compounds like aldehydes or ketones. Acetals are unaffected by bases, nucleophiles, oxidizing agents, and reducing agents. They serve as protecting groups for aldehydes and ketones. Acetals can be easily formed and also easily removed via mild acid hydrolysis.
In the presence of multiple functional groups, when selective reduction of one group over the other is desired, groups like aldehydes and ketones that form acetals...