TY  - JOUR
A1  - Schmidt, Marco F.
A1  - Korb, Oliver
A1  - Abell, Chris
T1  - Antagonists of the miRNA-Argonaute 2 Protein Complex
BT  - Anti-miR-AGOs
JF  - Drug Target miRNA: Methods and Protocols
N2  - microRNAs (miRNAs) have been identified as high-value drug targets. A widely applied strategy in miRNA inhibition is the use of antisense agents. However, it has been shown that oligonucleotides are poorly cell permeable because of their complex chemical structure and due to their negatively charged backbone. Consequently, the general application of oligonucleotides in therapy is limited. Since miRNAs’ functions are executed exclusively by the Argonaute 2 protein, we therefore describe a protocol for the design of a novel miRNA inhibitor class: antagonists of the miRNA-Argonaute 2 protein complex, so-called anti-miR-AGOs, that not only block the crucial binding site of the target miRNA but also bind to the protein’s active site. Due to their lower molecular weight and, thus, more drug-like chemical structure, the novel inhibitor class may show better pharmacokinetic properties than reported oligonucleotide inhibitors, enabling them for potential therapeutic use.
KW  - Drug design
KW  - microRNA
KW  - miRNA-Argonaute 2 protein complex
KW  - miRNA inhibitors
KW  - miRNA seed region
Y1  - 2016
SN  - 978-1-4939-6563-2
SN  - 978-1-4939-6561-8
SN  - 978-1-4939-8236-3
U6  - https://doi.org/10.1007/978-1-4939-6563-2_17
SN  - 1064-3745
SN  - 1940-6029
VL  - 1517
SP  - 239
EP  - 249
PB  - Springer
CY  - New York
ER  -