Template-directed ligation of peptides to oligonucleotides
Template-directed ligation of peptides to oligonucleotides
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DOI：
10.1016/s1074-5521(96)90084-8
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发表时间：
1996-01-01
影响因子：
--
通讯作者：
Joyce, GF
中科院分区：
文献类型：
--
作者：
Bruick, RK;Dawson, PE;Joyce, GF
背景：寡核苷酸-肽缀合物有几种应用，包括它们作为治疗剂的潜在用途。我们开发了一种在水溶液中无保护肽与寡核苷酸的化学连接策略。这两个化合物通过一个稳定的酰胺键在模板导向反应中连接。结果：以羧基端硫酯结尾的多肽被转化为硫酯连接的寡核苷酸肽中间体。中间体的寡核苷酸部分结合到互补的寡核苷酸模板上，使肽靠近以3'胺为末端的邻近模板结合的寡核苷酸。随后的反应结果是有效地形成酰胺连接的寡核苷酸-肽缀合物。结论：寡核苷酸模板可以通过一个高度稳定的酰胺连接来指导肽与寡核苷酸的连接。连接反应是序列特异性的，允许同时连接多个寡核苷酸-肽对。
Background: Oligonucleotide-peptide conjugates have several applications, including their potential use as therapeutic agents. We developed a strategy for the chemical ligation oi unprotected peptides to oligonucleotides in aqueous solution. The two compounds are joined via a stable amide bond in a template-directed reaction.Results: Peptides, ending in a carboxy-terminal thioester, were converted to thio ester-linked oligonucleotide-peptide intermediates. The oligonucleotide portion of the intermediate binds to a complementary oligonucleotide template, placing the peptide in close proximity to an adjacent template-bound oligonucleotide that terminates in a 3' amine. The ensuing reaction results ill the efficient formation of an amide-linked oligonucleotide-peptide conjugate.Conclusions: An oligonucleotide template can be used to direct the ligation of peptides to oligonucleotides via a highly stable amide linkage. The ligation reaction is sequence-specific, allowing the simultaneous Ligation of multiple oligonucleotide-peptide pairs.