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In Vivo Targeting Using Arylboronate/Nopoldiol Click Conjugation.
Palvai, Sandeep; Bhangu, Jasmine; Akgun, Burcin; Moody, Christopher T; Hall, Dennis G; Brudno, Yevgeny.
Afiliação
  • Palvai S; Joint Department of Biomedical Engineering, University of North Carolina - Chapel Hill and North Carolina State University Raleigh, 1840 Entrepreneur Drive, Raleigh, North Carolina 27695, United States.
  • Bhangu J; Department of Chemistry, University of Alberta, Edmonton, Alberta T6G 2G2, Canada.
  • Akgun B; Department of Chemistry, University of Alberta, Edmonton, Alberta T6G 2G2, Canada.
  • Moody CT; Joint Department of Biomedical Engineering, University of North Carolina - Chapel Hill and North Carolina State University Raleigh, 1840 Entrepreneur Drive, Raleigh, North Carolina 27695, United States.
  • Hall DG; Department of Chemistry, University of Alberta, Edmonton, Alberta T6G 2G2, Canada.
  • Brudno Y; Joint Department of Biomedical Engineering, University of North Carolina - Chapel Hill and North Carolina State University Raleigh, 1840 Entrepreneur Drive, Raleigh, North Carolina 27695, United States.
Bioconjug Chem ; 31(10): 2288-2292, 2020 10 21.
Article em En | MEDLINE | ID: mdl-32960584
Bioorthogonal click reactions yielding stable and irreversible adducts are in high demand for in vivo applications, including in biomolecular labeling, diagnostic imaging, and drug delivery. Previously, we reported a novel bioorthogonal "click" reaction based on the coupling of ortho-acetyl arylboronates and thiosemicarbazide-functionalized nopoldiol. We now report that a detailed structural analysis of the arylboronate/nopoldiol adduct by X-ray crystallography and 11B NMR reveals that the bioorthogonal reactants form, unexpectedly, a tetracyclic adduct through the cyclization of the distal nitrogen into the semithiocarbazone leading to a strong B-N dative bond and two new 5-membered rings. The cyclization adduct, which protects the boronate unit against hydrolytic breakdown, sheds light on the irreversible nature of this polycondensation. The potential of this reaction to work in a live animal setting was studied through in vivo capture of fluorescently labeled molecules in vivo. Arylboronates were introduced into tissues through intradermal injection of their activated NHS esters, which react with amines in the extracellular matrix. Fluorescently labeled nopoldiol molecules were administered systemically and were efficiently captured by the arylboronic acids in a location-specific manner. Taken together, these in vivo proof-of-concept studies establish arylboronate/nopoldiol bioorthogonal chemistry as a candidate for wide array of applications in chemical biology and drug delivery.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Semicarbazidas / Ácidos Borônicos Limite: Animals Idioma: En Revista: Bioconjug Chem Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Semicarbazidas / Ácidos Borônicos Limite: Animals Idioma: En Revista: Bioconjug Chem Ano de publicação: 2020 Tipo de documento: Article