A flow platform for degradation-free CuAAC bioconjugation

被引：47

作者：

Hatit, Marine Z. C. ^{[1
]}

Reichenbach, Linus F. ^{[1
]}

Tobin, John M. ^{[2
]}

Vilela, Filipe ^{[2
]}

Burley, Glenn A. ^{[1
]}

Watson, Allan J. B. ^{[3
]}

机构：

[1] Univ Strathclyde, Dept Pure & Appl Chem, 295 Cathedral St, Glasgow G1 1XL, Lanark, Scotland

[2] Heriot Watt Univ, Chem Sci, Edinburgh EH14 4AS, Midlothian, Scotland

[3] Univ St Andrews, Sch Chem, St Andrews KY16 9ST, Fife, Scotland

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

英国生物技术与生命科学研究理事会;

关键词：

AZIDE-ALKYNE CYCLOADDITION; CLICK CHEMISTRY; BIOORTHOGONAL REACTIONS; LIGATION; DELIVERY; CELLS; FUNCTIONALIZATION; OLIGONUCLEOTIDES; REACTIVITY; PEPTIDES;

D O I：

10.1038/s41467-018-06551-0

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The Cu-catalyzed azide-alkyne cycloaddition (CuAAC) reaction is a cornerstone method for the ligation of biomolecules. However, undesired Cu-mediated oxidation and Cu-contamination in bioconjugates limits biomedical utility. Here, we report a generic CuAAC flow platform for the rapid, robust, and broad-spectrum formation of discrete triazole bioconjugates. This process leverages an engineering problem to chemical advantage: solvent-mediated Cu pipe erosion generates ppm levels of Cu in situ under laminar flow conditions. This is sufficient to catalyze the CuAAC reaction of small molecule alkynes and azides, fluorophores, marketed drug molecules, peptides, DNA, and therapeutic oligonucleotides. This flow approach, not replicated in batch, operates at ambient temperature and pressure, requires short residence times, avoids oxidation of sensitive functional groups, and produces products with very low ppm Cu contamination.

引用

页数：7

共 51 条

[1] Measuring and Suppressing the Oxidative Damage to DNA During Cu(I)-Catalyzed Azide-Alkyne Cycloaddition [J].

Abel, Gary R., Jr. ;

Calabrese, Zachary A. ;

Ayco, Jeffrey ;

Hein, Jason E. ;

Ye, Tao .

BIOCONJUGATE CHEMISTRY, 2016, 27 (03) :698-704

[2]

Barnes JC, 2015, NAT CHEM, V7, P810, DOI [10.1038/NCHEM.2346, 10.1038/nchem.2346]

[3] Copper-free click chemistry for dynamic in vivo imaging [J].

Baskin, Jeremy M. ;

Prescher, Jennifer A. ;

Laughlin, Scott T. ;

Agard, Nicholas J. ;

Chang, Pamela V. ;

Miller, Isaac A. ;

Lo, Anderson ;

Codelli, Julian A. ;

Bertozzi, Carolyn R. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (43) :16793-16797

[4] Tetrazine ligation: Fast bioconjugation based on inverse-electron-demand Diels-Alder reactivity [J].

Blackman, Melissa L. ;

Royzen, Maksim ;

Fox, Joseph M. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2008, 130 (41) :13518-+

[5] Efficient Access to New Chemical Space Through Flow-Construction of Druglike Macrocycles Through Copper-Surface-Catalyzed Azide-Alkyne Cycloaddition Reactions [J].

Bogdan, Andrew R. ;

James, Keith .

CHEMISTRY-A EUROPEAN JOURNAL, 2010, 16 (48) :14506-14512

[6] The Use of Copper Flow Reactor Technology for the Continuous Synthesis of 1,4-Disubstituted 1,2,3-Triazoles [J].

Bogdan, Andrew R. ;

Sach, Neal W. .

ADVANCED SYNTHESIS & CATALYSIS, 2009, 351 (06) :849-854

[7] When CuAAC 'Click Chemistry' goes heterogeneous [J].

Chassaing, S. ;

Beneteau, V. ;

Pale, P. .

CATALYSIS SCIENCE & TECHNOLOGY, 2016, 6 (04) :923-957

[8] Fast and Sensitive Pretargeted Labeling of Cancer Cells through a Tetrazine/trans-Cyclooctene Cycloaddition [J].

Devaraj, Neal K. ;

Upadhyay, Rabi ;

Hatin, Jered B. ;

Hilderbrand, Scott A. ;

Weissleder, Ralph .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2009, 48 (38) :7013-7016

[9] Tetrazine-Based Cycloadditions: Application to Pretargeted Live Cell Imaging [J].

Devaraj, Neal K. ;

Weissleder, Ralph ;

Hilderbrand, Scott A. .

BIOCONJUGATE CHEMISTRY, 2008, 19 (12) :2297-2299

[10] Strain-Promoted 1,3-Dipolar Cycloaddition of Cycloalkynes and Organic Azides [J].

Dommerholt, Jan ;

Rutjes, Floris P. J. T. ;

van Delft, Floris L. .

TOPICS IN CURRENT CHEMISTRY, 2016, 374 (02)

← 1 2 3 4 5 6 →