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Chemoselective modification of specific residues within a given protein poses a significant challenge, as the microenvironment of amino acid residues in proteins is variable. Developing a universal molecular platform with tunable chemical warheads can provide powerful tools for precisely labeling specific amino acids in proteins. Cysteine and lysine are hot targets for chemoselective modification, but current cysteine/lysine‐selective warheads face challenges due to cross‐reactivity and unstable reaction products. In this study, a versatile fluorescent platform is developed for highly selective modification of cysteine/lysine under biocompatible conditions. Chloro‐ or phenoxy‐substituted NBSe derivatives effectively labeled cysteine residues in the cellular proteome with high specificity. This finding also led to the development of phenoxy‐NBSe phototheragnostic for the diagnosis and activatable photodynamic therapy of GSH‐overexpressed cancer cells. Conversely, alkoxy‐NBSe derivatives are engineered to selectively react with lysine residues in the cellular environment, exhibiting excellent anti‐interfering ability against thiols. Leveraging a proximity‐driven approach, alkoxy‐NBSe probes are successfully designed to demonstrate their utility in bioimaging of lysine deacetylase activity. This study also achieves integrating a small photosensitizer into lysine residues of proteins in a regioselective manner, achieving photoablation of cancer cells activated by overexpressed proteins. [ABSTRACT FROM AUTHOR]

One effective solution in the analysis of complex mixtures, including protein or cell hydrolysates, is based on chemoselective derivatization of a selected group of compounds by using selective tags to facilitate detection. Another method is based on the capture of the desired compounds by properly designed solid supports, resulting in sample enrichment. Cysteine is one of the rarest amino acids, but at least one cysteine residue is present in more than 91% of human proteins, which clearly confirms its important role in biological systems. Some cysteine-containing peptides may serve as significant molecular biomarkers, which may emerge as key indices in the management of patients with particular diseases. In the current review, we describe recent advances in the development of cysteine-containing peptide modification techniques based on solution and solid phase derivatization and enrichment strategies.

In recent years, there has been a growing demand for novel strategies for biomedical applications. Chitosan is a typical cationic amino-containing polysaccharide that has been widely used due to its unique properties. The grafting modification of chitosan has been explored as an interesting method to develop multifunctional novel chitosan hybrid materials for drug delivery, tissue engineering, and other biomedical applications. Recently, “click” chemistry has been introduced into the synthesis of polymeric materials with well-defined and complex chain architectures. The Huisgen’s 1,3-dipolar cycloaddition reaction between alkynes and azides yielding triazoles is the principal example of a “click” reaction. Bioconjugation, surface modification, and orthogonal functionalization of polymers were successfully performed through this chemoselective reaction. In recent literature interest has been shown in this cycloaddition for the modification of polysaccharides, however, only a few chitosan graft copolymers have been synthesized by this technique.

Copper-mediated coupling between alkynes to generate a structurally rigid, linear 1,3-diyne linkage has been known for over a century. However, the mechanistic requirement to simultaneously maintain CuI and an oxidant has limited its practical utility, especially for complex functional molecules in aqueous solution. We find that addition of a specific bpy-diol ligand protects unprotected peptides from CuII-mediated oxidative damage through the formation of an insoluble CuII gel which solves the critical challenge of applying Glaser coupling to substrates that are degraded by CuII. The generality of this method is illustrated through the conjugation of a series of polar and nonpolar labels onto a fully unprotected GLP-1R agonist through a linear 7 Å diynyl linker. [ABSTRACT FROM AUTHOR]

Abstract: A short synthesis of chemoselective chitosan derivatives was achieved by copper-catalyzed Huisgen cycloaddition, which is an ideal reaction for click chemistry, by using N-(4-azidophthaloyl)-chitosan. N-(4-azidophthaloyl)-chitosan was prepared through chemoselective N-bromophthaloylation of chitosan in acidic water and subsequent azidation. The obtained N-(4-bromopthaloyl)-chitosan had higher solubility in common solvents than conventional phthaloyl chitosan. N-(4-azidophthaloyl)-chitosan was successfully converted with ethynyl derivatives having functional groups (hydroxymethyl, phenyl, and methyl ester) in the presence of copper(II) sulfate, sodium ascorbate and/or trimethylamine. FT-IR spectra, elemental analyses, and 1H and 13C NMR spectra supported that the desired chitosan derivatives were chemoselectively transferred by these groups with a 1,4-triazole linker. [Copyright &y& Elsevier]

One effective solution in the analysis of complex mixtures, including protein or cell hydrolysates, is based on chemoselective derivatization of a selected group of compounds by using selective tags to facilitate detection. Another method is based on the capture of the desired compounds by properly designed solid supports, resulting in sample enrichment. Cysteine is one of the rarest amino acids, but at least one cysteine residue is present in more than 91% of human proteins, which clearly confirms its important role in biological systems. Some cysteine-containing peptides may serve as significant molecular biomarkers, which may emerge as key indices in the management of patients with particular diseases. In the current review, we describe recent advances in the development of cysteine-containing peptide modification techniques based on solution and solid phase derivatization and enrichment strategies. [ABSTRACT FROM AUTHOR]

M13 bacteriophage (phage) has emerged as an attractive bionanomaterial owing to its genetically tunable surface chemistry and its potential to self-assemble into hierarchical structures. Furthermore, because of its unique nanoscopic structure, phage has been proposed as a model system in soft condensed physics and as a biomimetic building block for structured functional materials. Genetic engineering of phage provides great opportunities to develop novel nanomaterials with functional surface peptide motifs; however, this biological approach is generally limited to peptides containing the 20 natural amino acids. To extend the scope of phage applications, strategies involving chemical modification have been employed to incorporate a wider range of functional groups, including synthetic chemical compounds. In this review, we introduce the design of chemoselective phage functionalization and discuss how such a strategy is combined with genetic engineering for a variety of medical applications, as reported in recent literature.