direct editing of cysteine to electrophilic alkyl halides in peptides vinyl thianthrenium - parabolic-peptides-review electrophilic Direct Editing of Cysteine to Electrophilic Alkyl Halides in Peptides: A Novel Approach to Peptide Modification

direct-peptide-co The ability to precisely modify peptides is a cornerstone of advancements in fields ranging from drug discovery to materials science. Among the 20 proteinogenic amino acids, cysteine stands out due to its unique thiol side chain, which offers a reactive handle for chemical functionalization. Historically, cysteine modification has relied on its nucleophilic character, reacting with electrophiles作者：F Xiang·2025—Among the 20 proteinogenic amino acids,cysteineis one of the most frequently targeted residues for chemical modification ofpeptidesand .... However, a significant breakthrough has emerged with methods that enable the direct editing of cysteine to electrophilic alkyl halides in peptides, effectively reversing the typical reactivity of the cysteine residue. This innovative approach, as detailed in recent research, allows for the direct conversion of the nucleophilic cysteine carbon–thiol side chain into an electrophilic carbon–halogen bond.

This development represents a powerful shift in peptide chemistry. Instead of cysteine acting as a nucleophile, it can be transformed into an electrophile, opening up new avenues for peptide modification and bioconjugation. The direct conversion of cysteine thiols into electrophilic carbon–halogen bonds provides a versatile platform for creating complex peptide structures and conjugates.Containing Peptides This strategy is particularly valuable for applications requiring precise control over peptide functionalization, such as the development of targeted therapeutics or the design of novel biomaterials.作者：M Kowalska·2022·被引用次数：5—Strong nucleophilic properties makecysteineeasily modified byelectrophilicand thiol-disulfide reagents. Several strategies of thiol-selective modification ...

The fundamental principle behind this direct editing strategy lies in an umpolung approach, where the inherent polarity of the cysteine residue is reversed.Photo‐and Electrochemical Modification of Amino Acids ... This allows for subsequent reactions with nucleophiles that would typically be incompatible with a free thiol. For instance, researchers have demonstrated that the nucleophilic cysteine carbon–thiol side chain can be directly converted into an electrophilic carbon–halogen bond. This transformation is crucial because it enables the peptide to react with a broad range of nucleophilic species that were previously inaccessible作者：AOY Chan·2013·被引用次数：60—A new approach for selective modification ofcysteine-containingpeptidesthrough gold-mediated oxidative allene–thiol coupling reaction in aqueous medium .... The resulting electrophilic site can then undergo substitution reactions with various nucleophiles, including carbon-based nucleophiles, leading to the formation of new carbon-carbon bonds.

One of the key advantages of this methodology is its chemoselectivityDirect Editing of Cysteine to Electrophilic Alkyl Halides in .... The direct editing process is designed to target the cysteine residue specifically, leaving other functional groups within the peptide intact. This high level of selectivity is essential for maintaining the structural integrity and biological activity of the peptide. Furthermore, the ability to directly functionalize cysteine residues in peptides simplifies synthetic routes and can lead to higher yields compared to multi-step procedures. The resulting electrophilic alkyl halides can then participate in diverse coupling reactions.

The implications of this direct editing of cysteine to electrophilic alkyl halides in peptides are far-reaching.Organometallic AlaM Reagents for Umpolung Peptide ... It offers a powerful tool for the synthesis of complex peptide conjugates, including those with modified amino acids or non-natural side chainsDirect Editing of Cysteine to Electrophilic Alkyl Halides in .... For example, this method can be used to introduce a variety of functional groups onto peptides, thereby enhancing their therapeutic properties or enabling their use in diagnostic applicationsChemo-selective modification of cysteine residue. The ability to create electrophilic sites on peptides also facilitates the development of novel crosslinking strategies, which are critical for stabilizing peptide structures or creating intricate molecular architectures.Direct Editing of Cysteine to Electrophilic Alkyl Halides in Peptides· Strategies and tactics for subcellular targeting of small molecule zinc sensors.

Beyond traditional peptide synthesis, this approach holds promise for post-translational mutagenesis and the installation of unnatural amino acids.2024年9月9日—This review provides a comprehensive overview of recent advancements in photo- and electrochemical approaches for the modification ofcysteineamino acid ... By enabling the precise modification of cysteine residues, researchers can introduce a wide array of chemical functionalities that are not found in nature. This opens up exciting possibilities for creating synthetic thiol and seleno derived amino acids for a variety of applications. The direct conversion of cysteine thiols into electrophilic carbon–halogen bonds represents a significant step forward in our ability to engineer peptides with tailored properties and functions. This advancement is set to accelerate progress in numerous areas of chemical biology and medicinal chemistry.