A bioorthogonal chemical reporter for the detection and identification of protein lactylation

Abstract

YnLac is an alkynyl-functionalized l-lactate analogue that is metabolically incorporated into l-lactylated proteins in live cells, enabling the fluorescence detection and proteomic identification of novel l-lactylated proteins.

Protein acylation: mechanisms, biological functions and therapeutic targets

“… 232 With the help of other chemical tools such as alkynyl-functionalized bioorthogonal chemical reporter (YnLac), nonhistone Klac has also been reported by other studies in recent years. 233 , 234 The limited studies on nonhistone Klac have indicated its critical role in tumor, polymicrobial sepsis and retinopathy.…”

A chemical probe for proteomic analysis and visualization of intracellular localization of lysine-succinylated proteins

“…In addition, various reporter mole-cules such as fluorescent dyes and biotin can be orthogonally labeled on the tag sites via Click chemistry (copper(I)-catalyzed alkyne-azide cycloaddition, CuAAC reaction), making it possible to realize selective enrichment and visualization of metabolically tagged proteins. Despite these advantages, only a few substrates have been developed to metabolically tag acylated proteins, [27][28][29][30] and no substrates are available for lysine succinylation. Therefore, we aimed to develop a new substrate that enables comprehensive analysis of succinylated proteins and visualization of their intracellular distribution, which will contribute to unveiling the previously unknown phenomenon of protein succinylation.…”

The role and mechanism of histone lactylation in health and diseases

“…Furthermore, lactylation modifications have primarily been studied on histones as of late, but we hypothesize that lactylation also occurs on non-histone proteins, similar to other modifications such as crotonylation. Additionally, the “YnLac” chemical reporter, which has an alkynyl functionalized bioorthogonal structure, may detect new lactylation modification sites in non-histone proteins ( Sun et al, 2022 ). In addition, several microbes and plants have also been identified with lactylated global proteins, including non-histone ( Gao et al, 2020 ; Zhang et al, 2021a ; Meng et al, 2021 ; Sun et al, 2022 ).…”

“…Additionally, the “YnLac” chemical reporter, which has an alkynyl functionalized bioorthogonal structure, may detect new lactylation modification sites in non-histone proteins ( Sun et al, 2022 ). In addition, several microbes and plants have also been identified with lactylated global proteins, including non-histone ( Gao et al, 2020 ; Zhang et al, 2021a ; Meng et al, 2021 ; Sun et al, 2022 ). On the other hand, there are currently no investigations of non-histone lactylation in mammals, and additional research is required.…”