期刊
CHEMISTRY-A EUROPEAN JOURNAL
卷 26, 期 66, 页码 15226-15231出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.202002675
关键词
67LR; bioconjugation; boronic acids; iminoboronate; laminin
资金
- Fundacao para a Ciencia e Tecnologia (FCT) [PTDC/QEQ-QOR/3644/2014, PTDC/QUI-QOR/29967/2017, LISBOA-01-0145-FEDER-029967, SAICTPAC/0019/2015, UIDB/04138/2020, UIDP/04138/2020]
- FCT [SAICTPAC/0019/2015, UID/QUI/00100/2013, PPBI-POCI-01-0145-FEDER-022122, IF/00386/2015]
- European Structural AMP
- Investment Funds through the COMPETE Programme
- Agencia Estatal de Investigacion [RTI2018-099592-B-C21]
- Fundação para a Ciência e a Tecnologia [PTDC/QUI-QOR/29967/2017, PTDC/QEQ-QOR/3644/2014] Funding Source: FCT
Boronic acids (BAs) are a promising bioconjugation function to design dynamic materials as they can establish reversible covalent bonds with oxygen/nitrogen nucleophiles that respond to different pH, ROS, carbohydrates and glutathione levels. However, the dynamic nature of these bonds also limits the control over the stability and site-selectivity of the bioconjugation, which ultimately leads to heterogeneous conjugates with poor stability under physiological conditions. Here we disclose a new strategy to install BAs on peptide chains. In this study, a boron hot spot based on the 3-hydroxyquinolin-2(1H)-one scaffold was developed and upon installation on a peptide N-terminal cysteine, enables the site-selective formation of iminoboronates with 2-formyl-phenyl boronic acids (K(a)of 58128 +/- 2 m(-1)). The reaction is selective in the presence of competing lysine epsilon-amino groups, and the resulting iminoboronates, displayed improved stability in buffers solutions and a cleavable profile in the presence of glutathione. Once developed, the methodology was used to prepare cleavable fluorescent conjugates with a laminin fragment, which enabled the validation of the 67LR receptor as a target to deliver cargo to cancer HT29 cells.
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