Category Ranking

98%

Total Visits

921

Avg Visit Duration

2 minutes

Citations

20

Article Abstract

While metabolites derived from gut microbiota metabolism have been linked to disease development in the human host, the chemical tools required for their detailed analysis and the discovery of biomarkers are limited. A unique and multifunctional chemical probe for mass spectrometric analysis, which contains p-nitrocinnamyloxycarbonyl as a new bioorthogonal cleavage site has been designed and synthesized. Coupled to magnetic beads, this chemical probe allows for straightforward extraction of metabolites from human samples and release under mild conditions. This isolation from the sample matrix results in significantly reduced ion suppression, an increased mass spectrometric sensitivity, and facilitates the detection of metabolites in femtomole quantities. The chemoselective probe was applied to the analysis of human fecal samples, resulting in the discovery of four metabolites previously unreported in this sample type and confirmation of the presence of medically relevant gut microbiota-derived metabolites.

Download full-text PDF

Source
http://dx.doi.org/10.1002/anie.201804828DOI Listing

Publication Analysis

Top Keywords

chemoselective probe
8
bioorthogonal cleavage
8
cleavage site
8
gut microbiota
8
microbiota metabolism
8
chemical probe
8
mass spectrometric
8
metabolites
5
probe unique
4
unique bioorthogonal
4

Similar Publications

Advances in click chemistry for drug discovery and development.

Expert Opin Drug Discov

August 2025

Department of Medicinal Chemistry, Shandong Key Laboratory of Druggability Optimization and Evaluation for Lead Compounds, School of Pharmaceutical Sciences, Cheeloo College of Medicine Shandong University, Jinan, Shandong, PR China.

Introduction: Click chemistry, first introduced by Sharpless and colleagues in 2001, has been an essential tool of drug research owing to its modularity, high efficiency, excellent yields, chemoselectivity, and mild reaction conditions.

Areas Covered: This review provides an overview of recent advances in drug development based on click chemistry over the past five years. It highlights key applications including fluorescent probes, lead identification and optimization, drug delivery systems, as well as emerging therapeutic modalities such as antibody-drug conjugates and protein degraders.

View Article and Find Full Text PDF

Chemoselective Installation of Electrophilic Warheads onto C-Terminal Peptide Hydrazides for Covalent Protease Inhibitor Synthesis.

ACS Chem Biol

August 2025

Laboratory for Organic Chemistry, Department of Chemistry and Applied Biosciences, ETH Zürich, 8093 Zürich, Switzerland.

Covalent binders to protein targets offer a powerful approach to the generation of tool compounds and an increasingly common strategy for therapeutic development. The installation of electrophiles onto peptide binders, however, is often precluded by standard conditions for peptide synthesis, which involve strong nucleophiles, bases, and acids. The introduction of C-terminal electrophiles is further complicated by the C → N directionality of standard solid-phase peptide synthesis.

View Article and Find Full Text PDF

Fatty acid esters of hydroxy fatty acids (FAHFAs) are emerging bioactive lipids in edible oils, but their trace-level presence and matrix complexity hinder accurate analysis. Here, we designed a novel chemoselective probe piperazine-modified silica () that specifically captures FAHFAs while removing almost totally triglycerides in a one-step labeling reaction. The probe enabled single-batch sample pretreatment within 30 min, integrating capture, purification, and signal amplification.

View Article and Find Full Text PDF

A High-Throughput Platform Utilizing FPBG-PITC for Amino-Containing Metabolites Screening in Breast Diseases.

Small Methods

July 2025

Department of Biophysics and Structural Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China.

Amino-containing metabolites play essential roles in biological processes such as protein synthesis and energy metabolism, and their dysregulation is associated with disease development. Liquid biopsy, valued for its minimal invasiveness, is widely utilized in cancer detection. However, traditional methods necessitate protein and lipid removal while suffering from low throughput and sensitivity.

View Article and Find Full Text PDF

The synthesis of neoglycoconjugates has paved the way for the discovery of novel probes that mimic natural glycoconjugates and can provide designed research tools and therapeutics. In some cases, the target protein may not be amenable to harsh conditions; therefore, semisynthetic or chemical methods must be chosen with care. Here, we present a simple and modular chemoselective coupling strategy between an unprotected sugar and an ,-disubstituted hydroxylamine under mild acidic conditions.

View Article and Find Full Text PDF