ABSTRACT
Covalently modified drugs,which exert their pharmacological effects by covalently binding to the targets,have been avoided as far as possible for a long time in drug design due to the potential off-target effects and other side-effects.With the in-depth study of binding modes of market blockbuster covalent drugs,more and more attention has been concentrated on covalently modified drugs.Current challenges remain in development of potent selective covalently modified drugs with fewer adverse effects.This paper reviews the classification of some covalently modified drugs,the drug-target binding modes and the new strategies of designing covalently modified drugs,in order to provide reference for rational design of covalent drugs.
ABSTRACT
Riboswitch is a novel type of posttranscriptional regulatory elements discovered by Breaker et al. in 2002. It can regulate gene expression by binding directly to small metabolites without the aid of protein molecules. Compared to normal protein-mediated regulation, riboswitch responds to metabolites more rapidly and sensitively. Its discovery opens a new world for RNA research. The recent advances in riboswitch researches were summarized, including crystal structure determination, mechanism and dynamics study, biosensor and antibacterial drug design. Topp et al. successfully reprogrammed E. coli to detect, follow, and precisely localize to a completely new chemical signal by using a synthetic riboswitch. This work provided new ideas for synthetic biology and artificial biology network. The advances in riboswitch 3D structure determination, reaction mechanism and dynamics provide useful information for rational drug design towards new generation of riboswitch-targeting antibacterials.