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Advancing Nitrile-Aminothiol Strategy for Dual and Sequential Bioconjugation.
Thombare, Varsha J; Wu, Yimin; Pamulapati, Kavya; Han, Meiling; Tailhades, Julien; Cryle, Max J; Roberts, Kade D; Velkov, Tony; Li, Jian; Patil, Nitin A.
Afiliación
  • Thombare VJ; Department of Pharmacology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 3800, Australia.
  • Wu Y; Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 3800, Australia.
  • Pamulapati K; Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 3800, Australia.
  • Han M; Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 3800, Australia.
  • Tailhades J; Department of Biochemistry Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 3800, Australia.
  • Cryle MJ; ARC Centre of Excellence for Innovations in Peptide and Protein Science, Australia.
  • Roberts KD; Department of Biochemistry Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 3800, Australia.
  • Velkov T; ARC Centre of Excellence for Innovations in Peptide and Protein Science, Australia.
  • Li J; Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 3800, Australia.
  • Patil NA; Department of Pharmacology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 3800, Australia.
Chemistry ; 30(46): e202401674, 2024 Aug 19.
Article en En | MEDLINE | ID: mdl-38839567
ABSTRACT
Nitrile-aminothiol conjugation (NATC) stands out as a promising biocompatible ligation technique due to its high chemo-selectivity. Herein we investigated the reactivity and substrate scope of NAT conjugation chemistry, thus developing a novel pH dependent orthogonal NATC as a valuable tool for chemical biology. The study of reaction kinetics elucidated that the combination of heteroaromatic nitrile and aminothiol groups led to the formation of an optimal bioorthogonal pairing, which is pH dependent. This pairing system was effectively utilized for sequential and dual conjugation. Subsequently, these rapid (≈1 h) and high yield (>90 %) conjugation strategies were successfully applied to a broad range of complex biomolecules, including oligonucleotides, chelates, small molecules and peptides. The effectiveness of this conjugation chemistry was demonstrated by synthesizing a fluorescently labelled antimicrobial peptide-oligonucleotide complex as a dual conjugate to imaging in live cells. This first-of-its-kind sequential NATC approach unveils unprecedented opportunities in modern chemical biology, showcasing exceptional adaptability in rapidly creating structurally complex bioconjugates. Furthermore, the results highlight its potential for versatile applications across fundamental and translational biomedical research.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos / Compuestos de Sulfhidrilo / Nitrilos Límite: Humans Idioma: En Revista: Chemistry Asunto de la revista: QUIMICA Año: 2024 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos / Compuestos de Sulfhidrilo / Nitrilos Límite: Humans Idioma: En Revista: Chemistry Asunto de la revista: QUIMICA Año: 2024 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Alemania