A succinyl lysine-based photo-cross-linking peptide probe for Sirtuin 5

A succinylation-specific photo-cross-linking peptide probe has been developed for the NAD+-dependent hydrolase Sirtuin 5.</p

Rapid synthesis of Abelson tyrosine kinase inhibitors using click chemistry

10.1039/b913333jOrganic and Biomolecular Chemistry7245129-513

Target profiling of zerumbone using a novel cell-permeable clickable probe and quantitative chemical proteomics

The first target profile for zerumbone in live cancer cells determined through quantitative competitive chemical proteomics with a cell-permeable probe.</p

The use of click chemistry in the emerging field of catalomics

10.1039/b923331hOrganic and Biomolecular Chemistry881749-176

Discovery of Leishmania Druggable Serine Proteases by Activity-Based Protein Profiling

Leishmaniasis are a group of diseases caused by parasitic protozoa of the genus Leishmania. Current treatments are limited by difficult administration, high cost, poor efficacy, toxicity, and growing resistance. New agents, with new mechanisms of action, are urgently needed to treat the disease. Although extensively studied in other organisms, serine proteases (SPs) have not been widely explored as antileishmanial drug targets. Herein, we report for the first time an activity-based protein profiling (ABPP) strategy to investigate new therapeutic targets within the SPs of the Leishmania parasites. Active-site directed fluorophosphonate probes (rhodamine and biotin-conjugated) were used for the detection and identification of active Leishmania serine hydrolases (SHs). Significant differences were observed in the SHs expression levels throughout the Leishmania life cycle and between different Leishmania species. Using iTRAQ-labelling-based quantitative proteomic mass spectrometry, we identified two targetable SPs in Leishmania mexicana: carboxypeptidase LmxM.18.0450 and prolyl oligopeptidase LmxM.36.6750. Druggability was ascertained by selective inhibition using the commercial serine protease inhibitors chymostatin, lactacystin and ZPP, which represent templates for future anti-leishmanial drug discovery programs. Collectively, the use of ABPP method complements existing genetic methods for target identification and validation in Leishmania

Global profiling of protein lipidation using chemical proteomic technologies

Protein lipidation is unique amongst post-translational modifications (PTMs) in enabling direct interaction with cell membranes, and is found in every form of life. Lipidation is important in normal function and in disease, but its intricate interplay with disease context presents a challenging for drug development. Global whole-proteome profiling of protein lipidation lies beyond the range of standard methods, but is well-suited to metabolic tagging with small ‘clickable’ chemical reporters that do not disrupt metabolism and function; chemoselective reactions are then used to add multifunctional labels exclusively to tagged-lipidated proteins. This chemical proteomic technology has opened up the first quantitative whole-proteome studies of the known major classes of protein lipidation, and the first insights into their full scope in vivo

Small molecule probes that target Ablkinase

10.1039/b919888aChemical Communications4671118-1120CHCO

High-throughput synthesis of azide libraries suitable for direct “click” chemistry and in situ screening

10.1039/b902338kOrganic and Biomolecular Chemistry791821-182