Тип публикации: статья из журнала
Год издания: 2021
Идентификатор DOI: 10.1016/j.omtn.2021.07.015
Ключевые слова: aptamer, fragment molecular orbital, lung adenocarcinoma, molecular dynamics, molecular simulations, oligonucleotide, saxs, small-angle x-ray scattering, spatial structure, tertiary structure
Аннотация: 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 increasingПоказать полностьюaptamer 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. © 2021
Журнал: Molecular Therapy - Nucleic Acids
Выпуск журнала: Vol. 25
Номера страниц: 316-327
ISSN журнала: 21622531
Издатель: Cell Press