APTA-MINILEGO FOR THROMBIN INHIBITORS: NEW INSIGHTS INTO NANO-MODULE CONSTRUCTION
Alexey Kopylov, Elena Zavyalova, Andrey Golovin, Roman Reshetnikov, Ekaterina Lapsheva, Timur Turchaninov, Alina Yuminova, and Galina Pavlova
Apto-Pharm Ltd., Chemistry Department, Department of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russian Federation
Nucleic Acid Aptamers are promising alternative to antibodies in fast growing enabling technology - theranostics. Set of DNA aptamers for human thrombin (thrombin binding aptamers, TBAs) have been developed by combinatorial library selection (SELEX), though there is still no rationale for the ‘Structure-Function’. All aptamers have putative pharmacophore - 15mer G-quadruplex motif linked to short duplex: 31-mer TBA31 and 26-mer NU172. In addition we have design novel modular DNA aptamer, RA36, with improved characteristics. All aptamers are covered by patents. Newly developed thrombin activity assay, as well as specific kinetics calculations, has been developed. Inhibition constant and types of inhibiting have been measured for the initial aptamers, and for a set of constructs having different combination of the structural modules like G-quadruplex, duplex and its conjunctions. Analysis of impact of module arrangement on functional activity has revealed rules for permitted combinations.