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Abstract: The site‐selective functionalization of unactivated C(sp3)−H bonds remains one of the greatest challenges in organic synthesis. Herein, we report on the site‐selective δ‐C(sp3)−H alkylation of amino acids and peptides with maleimides via a kinetically less favored six‐membered palladacycle in the presence of more accessible γ‐C(sp3)−H bonds. Experimental studies revealed that C−H bond cleavage occurs reversibly and preferentially at γ‐methyl over δ‐methyl C−H bonds while the subsequent alkylation proceeds exclusively at the six‐membered palladacycle that is generated by δ‐C−H activation. The selectivity can be explained by the Curtin–Hammett principle. The exceptional compatibility of this alkylation with various oligopeptides renders this procedure valuable for late‐stage peptide modifications. Notably, this process is also the first palladium(II)‐catalyzed Michael‐type alkylation reaction that proceeds through C(sp3)−H activation. [ABSTRACT FROM AUTHOR]

Sessile organisms have undergone long-term evolution to develop the unique ability by positioning themselves on wet solid surface through secreting adhesive proteins. The present study reveals that natural amino acid monomers can also exhibit similar adhesion capacity. This kind of biomimetic adhesives were created by the one-step aqueous assembly of basic amino acids with assistance of anionic polyoxometalates. The polyoxometalates not only serve as multivalent scaffold to initiate the supramolecular cross-linking of amino acid molecules, but also function as a redox component, bestowing the wet adhesives with electrochromic features. [ABSTRACT FROM AUTHOR]

The selective generation of covalent bonds between and within proteins would provide new avenues for studying protein function and engineering proteins with new properties. New covalent bonds were genetically introduced into proteins by enabling an unnatural amino acid (Uaa) to selectively react with a proximal natural residue. This proximity-enabled bioreactivity was expanded to a series of haloalkane Uaas. Orthogonal tRNA/synthetase pairs were evolved to incorporate these Uaas, which only form a covalent thioether bond with cysteine when positioned in close proximity. By using the Uaa and cysteine, spontaneous covalent bond formation was demonstrated between an affibody and its substrate Z protein, thereby leading to irreversible binding, and within the affibody to increase its thermostability. This strategy of proximity-enabled protein crosslinking (PEPC) may be generally expanded to target different natural amino acids, thus providing diversity and flexibility in covalent bond formation for protein research and protein engineering. [ABSTRACT FROM AUTHOR]