期刊
MOLECULAR THERAPY-NUCLEIC ACIDS
卷 25, 期 -, 页码 316-327出版社
CELL PRESS
DOI: 10.1016/j.omtn.2021.07.015
关键词
-
资金
- Russian Science Founda-tion [21-73-20240]
- Russian Foundation for Basic Research [19-32-90266, 19-03-00043]
- JSPS KAKENHI [19H02682]
- BMBF [16QK10A]
- US Department of Energy, Office of Science [DE-AC02-06CH11357]
- Eu-ropean Union [H2020-INFRAEDI-02-2018-823830, H2020-EINFRA-2015-1-675728]
- Russian Science Foundation [21-73-20240] Funding Source: Russian Science Foundation
Aptamers, short DNA or RNA molecules, bind to target molecules with specificity, with affinity depending on their tertiary structure and charge distribution. Optimizing length and structure is crucial for improving aptamer specificity and affinity. LC-18t, a truncated version of aptamer LC-18, showed stronger binding to cancerous cells in lung tumor tissues and shared the binding site with the original aptamer.
Aptamers are short, single-stranded DNA or RNA oligonucleotide molecules that function as synthetic analogs of antibodies and bind to a target molecule with high specificity. Aptamer affinity entirely depends on its tertiary structure and charge distribution. Therefore, length and structure optimization are essential for increasing aptamer specificity and affinity. Here, we present a general optimization procedure for finding the most populated atomistic structures of DNA aptamers. Based on the existed aptamer LC-18 for lung adenocarcinoma, a new truncated LC-18 (LC-18t) aptamer LC-18t was developed. A three-dimensional (3D) shape of LC-18t was reported based on small-angle X-ray scattering (SAXS) experiments and molecular modeling by fragment molecular orbital or molecular dynamic methods. Molecular simulations revealed an ensemble of possible aptamer conformations in solution that were in close agreement with measured SAXS data. The aptamer LC-18t had stronger binding to cancerous cells in lung tumor tissues and shared the binding site with the original larger aptamer. The suggested approach reveals 3D shapes of aptamers and helps in designing better affinity probes.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据