Enhanced control of RNA modification and CRISPR-Cas activity through redox-triggered disulfide cleavage.

Chemical RNA modification has emerged as a flexible approach for post-synthetic modifications in chemical biology research. Guide RNA (gRNA) plays a crucial role in the clustered regularly interspaced short palindromic repeats and associated protein system (CRISPR-Cas). Several toolkits have been developed to regulate gene expression and editing through modifications of gRNA.

Chemical Control of CRISPR Gene Editing via Conditional Diacylation Crosslinking of Guide RNAs.

Conditional control of RNA structure and function has emerged as an effective toolkit. Here, a strategy based on a one-step introduction of diacylation linkers and azide groups on the 2'-OH of RNA is advance. Selected from eight phosphine reagents, it is found that 2-(diphenylphosphino)ethylamine has excellent performance in reducing azides via a Staudinger reduction to obtain the original RNA.

G-quadruplex-guided RNA engineering to modulate CRISPR-based genomic regulation.

It is important to develop small moelcule-based methods to modulate gene editing and expression in human cells. The roles of the G-quadruplex (G4) in biological systems have been widely studied. Here, G4-guided RNA engineering is performed to generate guide RNA with G4-forming units (G4-gRNA).

Bioactivatable reductive cleavage of azobenzene for controlling functional dumbbell oligodeoxynucleotides.

Application of stimuli-responsive bioactive molecules is an attractive strategy due to use for target special tissues and cells. Here, we reported synthesis of an azo-linker, 2,2'-dimethoxyl-4,4'-dihydroxymethylazobenzene (mAzo), which was more effectively recognized and cleaved by reducing glutathione (GSH) via comparing with 4,4'-dihydroxymethylazobenzene (Azo). In addition, mAzo is further exploited to engineer dumbbell asODNs, which could result in the release of asODNs and thus modulate their hybridization to target nucleic acids.

Design, synthesis and antitumor activity of Novel Sorafenib derivatives bearing pyrazole scaffold.

Four series of Sorafenib derivatives bearing pyrazole scaffold (8a-m, 9a-c, 10a-e and 11a) were synthesized and characterized by NMR and MS. All of the target compounds were evaluated for the cytotoxicity against A549, HepG2, MCF-7, and PC-3 cancer cell lines and some selected compounds were further evaluated for the activity against VEGFR-2/KDR, BRAF, CRAF, c-Met, EGFR and Flt-3 kinases. Compounds 8b and 8i were more active than that of compounds 8h, 9a, especially the IC value of compounds 8b on VEGFR-2 kinase was 0.