RESUMO
Late-stage specific and selective diversifications of peptides and proteins performed at target residues under ambient conditions are recognized to be the most facile route to various and abundant conjugates. Herein, we report an orthogonal modification of cysteine residues using alkyl thianthreium salts, which proceeds with excellent chemoselectivity and compatibility under mild conditions, introducing a diverse array of functional structures. Crucially, multifaceted bioconjugation is achieved through clickable handles to incorporate structurally diverse functional molecules. This "two steps, one pot" bioconjugation method is successfully applied to label bovine serum albumin. Therefore, our technique is a versatile and powerful tool for late-stage orthogonal bioconjugation.
Assuntos
Cisteína , Peptídeos , Soroalbumina Bovina , Cisteína/química , Peptídeos/química , Soroalbumina Bovina/química , Sais/química , Química Click/métodos , Animais , Proteínas/química , BovinosRESUMO
A method for introducing a range of phosphonates into oligopeptides through a Michael addition reaction between dehydroalanine and phosphite is presented. The method offers a mild, cheap, and straightforward approach to peptide phosphorylation that has potential applications in chemical biology and medicinal chemistry. Moreover, the introduction of a phosphonate group into short antibacterial peptides is described to demonstrate its utility, leading to the discovery of phosphonated antibacterial peptides with potent broad-spectrum antibacterial activity.
Assuntos
Alanina , Antibacterianos , Oligopeptídeos , Organofosfonatos , Fosfitos , Organofosfonatos/química , Organofosfonatos/síntese química , Oligopeptídeos/química , Fosfitos/química , Estrutura Molecular , Antibacterianos/química , Antibacterianos/farmacologia , Antibacterianos/síntese química , Alanina/química , Alanina/análogos & derivados , Testes de Sensibilidade Microbiana , FosforilaçãoRESUMO
Peptide and protein postmodification have gained significant attention due to their extensive impact on biomolecule engineering and drug discovery, of which cysteine-specific modification strategies are prominent due to their inherent nucleophilicity and low abundance. Herein, the study introduces a novel approach utilizing multifunctional 5-substituted 1,2,3-triazine derivatives to achieve multifaceted bioconjugation targeting cysteine-containing peptides and proteins. On the one hand, this represents an inaugural instance of employing 1,2,3-triazine in biomolecular-specific modification within a physiological solution. On the other hand, as a powerful combination of precision modification and biorthogonality, this strategy allows for the one-pot dual-orthogonal functionalization of biomolecules utilizing the aldehyde group generated simultaneously. 1,2,3-Triazine derivatives with diverse functional groups allow conjugation to peptides or proteins, while bi-triazines enable peptide cyclization and dimerization. The examination of the stability of bi-triazines revealed their potential for reversible peptide modification. This work establishes a comprehensive platform for identifying cysteine-selective modifications, providing new avenues for peptide-based drug development, protein bioconjugation, and chemical biology research.