Bruick R K, Dawson P E, Kent S B, Usman N, Joyce G F
The Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, CA 92037, USA.
Chem Biol. 1996 Jan;3(1):49-56. doi: 10.1016/s1074-5521(96)90084-8.
Oligonucleotide-peptide conjugates have several applications, including their potential use as therapeutic agents. We developed a strategy for the chemical ligation of unprotected peptides to oligonucleotides in aqueous solution. The two compounds are joined via a stable amide bond in a template-directed reaction.
Peptides, ending in a carboxy-terminal thioester, were converted to thioester-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 in the efficient formation of an amide-linked oligonucleotide-peptide conjugate.
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.
寡核苷酸 - 肽缀合物有多种应用，包括其作为治疗剂的潜在用途。我们开发了一种在水溶液中将未保护的肽化学连接到寡核苷酸的策略。这两种化合物通过模板导向反应中的稳定酰胺键连接在一起。
以羧基末端硫酯结尾的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与互补的寡核苷酸模板结合，使肽与以3'胺结尾的相邻模板结合的寡核苷酸紧密相邻。随后的反应导致高效形成酰胺连接的寡核苷酸 - 肽缀合物。
寡核苷酸模板可用于通过高度稳定的酰胺键将肽连接到寡核苷酸上。连接反应具有序列特异性，允许同时连接多个寡核苷酸 - 肽对。
