News & Comment

Mycobacteria produce carbohydrates of exceptional structures that are covalently modified by unique substituents, whose functional characterization could expand our understanding of how mycobacteria adapt to their environment.

Post-translational modifications (PTMs) are ubiquitous in all forms of life and often modulate critical protein functions. Recent chemical and biological advances have finally enabled scientists to precisely modify proteins at physiologically relevant positions, ushering in a new era of protein studies.

The central dogma processes of DNA replication, transcription, and translation are responsible for the maintenance and expression of every gene in an organism. An orthogonal central dogma may insulate genetic programs from host regulation and allow expansion of the roles of these processes within the cell.

Selection of molecular targets based on disease understanding is a dominant paradigm in drug discovery. We argue that a focus on classes of targets with central roles in biology provides a complementary approach that has higher quality outcomes in early discovery efforts.

To fully leverage the potential of human-induced pluripotent stem cells (hiPSCs), improved and standardized reprogramming methods and large-scale collections of hiPSC lines are needed, and the stem cell community must embrace chemical biology methodology for target identification and validation.

Cell-to-cell signaling networks, although poorly understood, guide tissue development, regulate tissue function and may become dysregulated in disease. Chemical biologists can develop the next generation of tools to untangle these complex and dynamic networks of interacting cells.

Nuclear magnetic resonance spectroscopy is transforming our views of proteins by revealing how their structures and dynamics are closely intertwined to underlie their functions and interactions. Compelling representations of proteins as statistical ensembles are uncovering the presence and biological relevance of conformationally heterogeneous states, thus gradually making it possible to go beyond the dichotomy between order and disorder through more quantitative descriptions that span the continuum between them.

Scientific convergence is a common theme of modern research, but undergraduate chemistry is commonly taught as an isolated discipline. Here we discuss curricular updates at three different institutions that are independently seeking to increase convergence in introductory chemistry courses.

Misregulated transcription factors play prominent roles in human disease, but their dynamic protein-protein interaction network has long made the goal of transcription-targeted therapeutics impractical. Recent advances in technologies for modulating protein interaction networks mean that the end of the quest is in sight.

X-ray crystallography, the workhorse of structural biology, has been revolutionized by the advent of serial femtosecond crystallography using X-ray free electron lasers. Here, the fast pace and history of discoveries are discussed together with current challenges and the method's great potential to make new structural discoveries, such as the ability to generate molecular movies of biomolecules at work.

A 'chemical biology of cellular membranes' must capture the way that mesoscale perturbations tune the biochemical properties of constituent lipid and protein molecules and vice versa. Whereas the classical paradigm focuses on chemical composition, dynamic modulation of the physical shape or curvature of a membrane is emerging as a complementary and synergistic modus operandi for regulating cellular membrane biology.

Protein kinases have emerged as one of the most successful families of drug targets. To date, most selective kinase inhibitors have been discovered serendipitously either through broad selectivity screening or through the discovery of unique binding modes. Here we discuss design strategies that could lead to a broader coverage of the kinome with selective inhibitors and to a more rational approach for developing them.

Chemical compounds designed to enhance understanding of host-pathogen interaction together with next-generation 'smart drugs' will rationally drive the discovery of promising new host-directed targets against pathogens including Mycobacterium tuberculosis, the causative agent of tuberculosis.

The recent emergence of signaling roles for transition metals presages a broader contribution of these elements beyond their traditional functions as metabolic cofactors. New chemical approaches to identify the sources, targets and physiologies of transition-metal signaling can help expand understanding of the periodic table in a biological context.

As the identification of previously undetected microbial biosynthetic pathways burgeons, there arises the question of how much new chemistry is yet to be found. This, in turn, devolves to: what kinds of biosynthetic enzymatic transformations are yet to be characterized?

A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.

Epigenetic chemical probes are having a strong impact in biological discovery and target validation. Systematic coverage of emerging epigenetic target classes with these potent, selective, cell-active chemical tools will profoundly influence understanding of the human biology and pathology of chromatin-templated mechanisms.

Chemical probes are powerful reagents with increasing impacts on biomedical research. However, probes of poor quality or that are used incorrectly generate misleading results. To help address these shortcomings, we will create a community-driven wiki resource to improve quality and convey current best practice.

Recent studies suggest that iron-sulfur (Fe-S) proteins may be unexpectedly abundant and functionally diverse in mammalian cells, but their identification still remains difficult. The use of informatics along with traditional spectroscopic analyses could be key to discovering new Fe-S proteins and validating their functional roles.

Enzymology has been a vital link between chemistry and biology in the second half of the twentieth century. A range of emerging scientific challenges is presenting the field with exciting opportunities to continue thriving in the future.