Сибирский федеральный университет

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 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. © 2021

Журнал: Molecular Therapy - Nucleic Acids

Выпуск журнала: Vol. 25

Номера страниц: 316-327

ISSN журнала: 21622531

Издатель: Cell Press

• Morozov Dmitry (Univ Jyvaskyla, Nanosci Ctr, POB 35, Jyvaskyla 40014, Finland; Univ Jyvaskyla, Dept Chem, POB 35, Jyvaskyla 40014, Finland)
• Mironov Vladimir (Lomonosov Moscow State Univ, Dept Chem, Moscow, Russia)
• Moryachkov Roman V. (Kirensky Inst Phys, Lab Phys Magnet Phenomena, 50-38 Akademgorodok, Krasnoyarsk 660036, Russia; RAS, SB, Fed Res Ctr, Krasnoyarsk Sci Ctr,Lab Digital Controlled Drugs, 50 Akademgorodok, Krasnoyarsk 660036, Russia)
• Shchugoreva Irina A. (RAS, SB, Fed Res Ctr, Krasnoyarsk Sci Ctr,Lab Digital Controlled Drugs, 50 Akademgorodok, Krasnoyarsk 660036, Russia; Krasnoyarsk State Med Univ, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia; Siberian Fed Univ, Dept Chem, 79 Svobodny Pr, Krasnoyarsk 660041, Russia)
• Artyushenko Polina V. (RAS, SB, Fed Res Ctr, Krasnoyarsk Sci Ctr,Lab Digital Controlled Drugs, 50 Akademgorodok, Krasnoyarsk 660036, Russia; Krasnoyarsk State Med Univ, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia; Siberian Fed Univ, Dept Chem, 79 Svobodny Pr, Krasnoyarsk 660041, Russia )
• Zamay Galina S. (RAS, SB, Fed Res Ctr, Krasnoyarsk Sci Ctr,Lab Digital Controlled Drugs, 50 Akademgorodok, Krasnoyarsk 660036, Russia; Krasnoyarsk State Med Univ, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia)
• Kolovskaya Olga S. (RAS, SB, Fed Res Ctr, Krasnoyarsk Sci Ctr,Lab Digital Controlled Drugs, 50 Akademgorodok, Krasnoyarsk 660036, Russia; Krasnoyarsk State Med Univ, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia)
• Zamay Tatiana N. (Krasnoyarsk State Med Univ, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia)
• Krat Alexey V. (Krasnoyarsk State Med Univ, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia)
• Molodenskiy Dmitry S. (European Mol Biol Lab, Hamburg Outstat, Notkestr 85, D-22603 Hamburg, Germany)
• Zabluda Vladimir N. (Kirensky Inst Phys, Lab Phys Magnet Phenomena, 50-38 Akademgorodok, Krasnoyarsk 660036, Russia)
• Veprintsev Dmitry V. (Krasnoyarsk State Med Univ, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia)
• Sokolov Alexey E. (Kirensky Inst Phys, Lab Phys Magnet Phenomena, 50-38 Akademgorodok, Krasnoyarsk 660036, Russia; RAS, SB, Fed Res Ctr, Krasnoyarsk Sci Ctr,Lab Digital Controlled Drugs, 50 Akademgorodok, Krasnoyarsk 660036, Russia)
• Zukov Ruslan A. (Krasnoyarsk State Med Univ, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia)
• Berezovski Maxim V. (Univ Ottawa, Dept Chem & Biomol Sci, 10 Marie Curie, Ottawa, ON K1N 6N5, Canada)
• Tomilin Felix N. (Kirensky Inst Phys, Lab Phys Magnet Phenomena, 50-38 Akademgorodok, Krasnoyarsk 660036, Russia; Siberian Fed Univ, Dept Chem, 79 Svobodny Pr, Krasnoyarsk 660041, Russia)
• Fedorov Dmitri G. (Natl Inst Adv Ind Sci & Technol, Res Ctr Computat Design Adv Funct Mat, Tsukuba, Ibaraki 3058568, Japan)
• Alexeev Yuri (Argonne Natl Lab, Comp Sci Div, Lemont, IL 60439 USA)
• Kichkailo Anna S. (RAS, SB, Fed Res Ctr, Krasnoyarsk Sci Ctr,Lab Digital Controlled Drugs, 50 Akademgorodok, Krasnoyarsk 660036, Russia; Krasnoyarsk State Med Univ, 1 Partizana Zheleznyaka, Krasnoyarsk 660022, Russia)

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