Oligonucleotide Bioconjugation with Bifunctional Palladium Reagents.
Oligonucleotide Bioconjugation with Bifunctional Palladium Reagents.
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DOI：
10.1002/anie.202103180
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发表时间：
2021-05-17
期刊：
影响因子：
--
通讯作者：
Pentelute BL
中科院分区：
文献类型：
--
作者：
Jbara M;Rodriguez J;Dhanjee HH;Loas A;Buchwald SL;Pentelute BL
有机金属试剂使生物偶联的实用策略成为可能。水溶性配体设计的创新和反应速率的提高使得多肽和蛋白质的化学选择性交叉偶联反应能够在水中进行。目前还没有基于有机金属的方法将寡核苷酸与其他生物分子进行生物偶联。本文报道了双功能钯(II)-氧化加成配合物（OACs）作为高产寡核苷酸生物偶联反应的试剂。这些双功能OACs与胺修饰的寡核苷酸发生化学选择性反应，生成第一个可分离的、稳定的寡核苷酸-钯（II） OACs。这些配合物在一小时内与低微摩尔浓度的天然含硫醇生物分子进行位点选择性C-S芳基化。该方法提供寡核苷酸-肽、寡核苷酸-蛋白、寡核苷酸-小分子和寡核苷酸-寡核苷酸偶联物，产率约为80%，并提供多拷贝寡核苷酸偶联到单克隆抗体上。连接生命分子。报道了通过双功能氧化加成络合物（OACs）快速和定点选择性的寡核苷酸生物偶联。这些双功能oac与胺修饰的寡核苷酸发生化学选择性反应，生成可分离的、稳定的寡核苷酸oac。在几分钟内，寡核苷酸oac在低微摩尔浓度下与广泛的天然含硫醇生物分子发生位点选择性C-S芳基化反应。
Organometallic reagents enable practical strategies for bioconjugation. Innovations in the design of water-soluble ligands and the enhancement of reaction rates have allowed for chemoselective cross-coupling reactions of peptides and proteins to be carried out in water. There are currently no organometallic-based methods for oligonucleotide bioconjugation to other biomolecules. Here we report bifunctional palladium(II)-oxidative addition complexes (OACs) as reagents for high-yielding oligonucleotide bioconjugation reactions. These bifunctional OACs react chemoselectively with amine-modified oligonucleotides to generate the first isolable, bench stable oligonucleotide-palladium(II) OACs. These complexes undergo site-selective C-S arylation with a broad range of native thiol-containing biomolecules at low micromolar concentrations in under one hour. This approach provided oligonucleotide-peptide, oligonucleotide-protein, oligonucleotide-small molecule, and oligonucleotide-oligonucleotide conjugates in >80% yield and afforded conjugation of multiple copies of oligonucleotides onto a monoclonal antibody. Linking life’s molecules. Rapid and site-selective oligonucleotide bioconjugation via bifunctional oxidative addition complexes (OACs) is reported. These bifunctional OACs react chemoselectively with amine-modified oligonucleotides to generate isolable, bench stable oligonucleotide OACs. Within minutes, the oligonucleotide OACs undergo a site-selective C-S arylation reaction with a broad range of native thiol-containing biomolecules at low micromolar concentrations.
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影响因子：
15
作者：
Dhanjee HH;Saebi A;Buslov I;Loftis AR;Buchwald SL;Pentelute BL
通讯作者：
Pentelute BL
影响因子：
16.6
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