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通过锁核酸(LNA)和α-L-锁核酸(α-l-LNA)取代改进链霉亲和素结合适体

Improvement of a streptavidin-binding aptamer by LNA- and α-l-LNA-substitutions.

作者信息

Jørgensen Anna S, Hansen Lykke H, Vester Birte, Wengel Jesper

机构信息

Nucleic Acid Center, Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark.

Nucleic Acid Center, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark.

出版信息

Bioorg Med Chem Lett. 2014 May 15;24(10):2273-7. doi: 10.1016/j.bmcl.2014.03.082. Epub 2014 Apr 3.

Abstract

Forty modified versions of a streptavidin-binding aptamer each containing single or multiple LNA or α-l-LNA-substitutions were synthesized and their dissociation constants determined by surface plasmon resonance experiments. Both full-length and truncated versions of the aptamer were studied and compared with the unmodified DNA aptamers. A ∼two-fold improvement in binding affinity was achieved by incorporation of LNA nucleotides in the 3'-part of the stems of the streptavidin-binding aptamer whereas LNA- and α-l-LNA-substitutions in the terminal stem increased the serum stability.

摘要

合成了四十种链霉亲和素结合适体的修饰变体,每个变体都含有单个或多个锁核酸(LNA)或α-L-锁核酸取代,并通过表面等离子体共振实验测定它们的解离常数。对适体的全长和截短版本都进行了研究,并与未修饰的DNA适体进行了比较。通过在链霉亲和素结合适体茎的3'部分掺入LNA核苷酸,结合亲和力提高了约两倍,而末端茎中的LNA和α-L-锁核酸取代提高了血清稳定性。

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