The growing demand for new therapeutic strategies in the medical and pharmaceutic fields has resulted in a pressing need for novel druggable targets.Paradoxically,however,the targets of certain drugs that are already widely used in clinical practice have largely not been annotated.Because the pharmacologic effects of a drug can only be appreciated when its interactions with cellular components are clearly delineated,an integrated deconvolution of drug-target interactions for each drug is necessary.The emerging field of chemical proteomics represents a powerful mass spectrometry(MS)-based affinity chromatography approach for identifying proteome-wide small molecule-protein interactions and mapping these interactions to signaling and metabolic pathways.This technique could comprehensively characterize drug targets,profile the toxicity of known drugs,and identify possible off-target activities.With the use of this technique,candidate drug molecules could be optimized,and predictable side effects might consequently be avoided.Herein,we provide a holistic overview of the major chemical proteomic approaches and highlight recent advances in this area as well as its potential applications in drug discovery.
Viruses replicate and proliferate in host cells while continuously adjusting to and modulating the host environment.They encode a wide spectrum of multifunctional proteins,which interplay with and modify proteins in host cells.Viral genomes were chronologically the first to be sequenced.However,the corresponding viral proteomes,the alterations of host proteomes upon viral infection,and the dynamic nature of proteins,such as post-translational modifications,enzymatic cleavage,and activation or destruction by proteolysis,remain largely unknown.Emerging high-throughput techniques,in particular quantitative or semi-quantitative mass spectrometry-based proteomics analysis of viral and cellular proteomes,have been applied to define viruses and their interactions with their hosts.Here,we review the major areas of viral proteomics,including virion proteomics,structural proteomics,viral protein interactomics,and changes to the host cell proteome upon viral infection.
The primary features of cancer are maintained via intrinsically modified metabolic activity, which is characterized by enhanced nutrient supply, energy production, and biosynthetic activity to synthesize a variety of macromolecular components during each passage through the cell cycle. This metabolic shift in transformed cells, as compared with non-proliferating cells, in-volves aberrant activation of aerobic glycolysis, de novo lipid biosynthesis and glutamine-dependent anaplerosis to fuel robust cell growth and proliferation. Here, we discuss the unique metabolic characteristics of cancer, the constitutive regulation of metabolism through a variety of signal transduction pathways and/or enzymes involved in metabolic reprogramming in cancer cells, and their implications in cancer diagnosis and therapy.
ZHOU ShengTao, HUANG CanHua & WEI YuQuan State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China
