Chaperonin Mechanisms: Multiple and (Mis)Understood?

The chaperonins are ubiquitous and essential nanomachines that assist in protein folding in an ATP-driven manner. They consist of two back-to-back stacked oligomeric rings with cavities in which protein (un)folding can take place in a shielding environment. This review focuses on GroEL from Escherichia coli and the eukaryotic chaperonin-containing t-complex polypeptide 1, which differ considerably in their reaction mechanisms despite sharing a similar overall architecture. Although chaperonins feature in many current biochemistry textbooks after being studied intensively for more than three decades, key aspects of their reaction mechanisms remain under debate and are discussed in this review. In particular, it is unclear whether a universal reaction mechanism operates for all substrates and whether it is passive, i.e., aggregation is prevented but the folding pathway is unaltered, or active. It is also unclear how chaperonin clients are distinguished from nonclients and what are the precise roles of the cofactors with which chaperonins interact. Expected final online publication date for the Annual Review of Biophysics, Volume 51 is May 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

7 Tetrazine-Based Cycloadditions in Click Chemistry

The spontaneous cycloaddition of tetrazines with a number of different dienophiles has become a powerful tool in chemical biology, in particular for the biocompatible conjugation and modification of (bio)molecules. The exceptional reaction kinetics made these bioorthogonal ligations the methods of choice for time-critical processes at very low concentrations, facilitating controlled molecular transformations in complex environments and even in vivo. The emerging concept of bond-cleavage reactions triggered by tetrazine-based cycloadditions enabled the design of diagnostic and therapeutic strategies. The tetrazine-triggered activation of prodrugs represents the first bioorthogonal reaction performed in humans, marking the beginning of the era of clinical translation of bioorthogonal chemistry. This chapter provides an overview of the synthesis and reactivity of tetrazines, their cycloadditions with various dienophiles, and transformations triggered by these reactions, focusing on reaction mechanisms, kinetics and efficiency, and selected applications.

Light alkane oxidation over well-defined active sites in metal–organic framework materials

We review structure–catalytic property relationships for MOF materials used in the direct oxidation of light alkanes, focusing specifically on the elucidation of active site structures and probes for reaction mechanisms.