Open AccessCyclic Peptidomimetics as Inhibitor for miR-155 Biogenesis
Author(s) -
Yan Hao,
Mi Zhou,
Umesh Bhattarai,
Yabin Song,
Mengmeng Zheng,
Jianfeng Cai,
FuSen Liang
Publication year - 2019
Publication title -
molecular pharmaceutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.13
H-Index - 127
eISSN - 1543-8392
pISSN - 1543-8384
DOI - 10.1021/acs.molpharmaceut.8b01247
Subject(s) - peptidomimetic , biogenesis , chemistry , small molecule , rna , in vitro , scaffold , computational biology , microbiology and biotechnology , biochemistry , biology , medicine , gene , peptide , biomedical engineering
miR-155 plays key promoting roles in several cancers and emerges as an important anticancer therapeutic target. However, the discovery of small molecules that target RNAs is challenging. Peptidomimetics have been shown to be a rich source for discovering novel ligands to regulate cellular proteins. However, the potential of using peptidomimetics for RNA targeting is relatively unexplored. To this end, we designed and synthesized members of a novel 320 000 compound macrocyclic peptidomimetic library. An affinity-based screening protocol led to the identification of a pre-miR-155 binder that inhibits oncogenic miR-155 maturation in vitro and in cell and induces cancer cell apoptosis. The results of this investigation demonstrate that macrocyclic peptidomimetics could serve as a new scaffold for RNA targeting.