First post from the Wang Lab

We will start a new experiment by asking students and postdocs to write blogs/previews for recent papers. This would be a good practice for their critical thinking and writing skills.

Here is a pretty good eBook "English Communication for Scientists" by Dr. Jean-luc Doumont.

I hope all the trainees in the lab will not only know how to do science but also learn how to communicate their science.

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Lysine-Targeted Covalent Inhibitors Gaining Traction

In the past decade, targeted covalent inhibitors (TCIs) has experienced a resurgence due to its sustained target engagement and improved proteome-wide selectivity. Currently, targeting cysteine residues with acrylamides and other α, β-unsaturated carbonyl compounds is the predominant strategy in TCI development. Although lysine is more prevalent than cysteine and possesses lower mutation rates, lysine has been much less frequently considered and more challenging as a residue targeted by TCIs due to its low nucleophilicity. Recently, Jack Taunton and his colleagues reveled their two related work in JACS . Based on the co-crystal structure of Hsp90 with a reversible inhibitor PU-H71, they designed two arylsulfonyl fluorides 1 and 2 and co-incubated them with Hsp90 protein (Figure 1a, b). Mass spectrometry detected the formation of a 1:1 covalent adduct. Mutation of Lys58 to arginine abrogated the covalent modification, indicating that the TCI selectively modified Lys58 (Fig...

Grafting Alkyne Handles on Cysteines

One of the most common ways to study biomolecules is to label specific amino acids, mostly cysteine, with chemical handles for further modification. Azide-alkyne click reaction is a very popular strategy due to its high reactivity and reaction rate. Therefore, numerous reagents have been developed to specifically label proteins with terminal alkynes, including iodoacetamide alkynes and maleimide derivatives. However, limitations like insufficient selectivity and low stability remain as long-lasting concerns. To address these problems, one common strategy is introducing a linker between the targeting residue and the alkyne moiety , which potentially brings in unwanted structural changes. A reagent that can introduce small-sized terminal alkyne with one step under mild conditions is in demand. Scheme 1 . Cysteine-labeling study in this work In this study, the Waser group presented a series of reagents that selectively ethynylate cysteine in a one-pot manner ( Scheme 1 ). The ...

First PROTAC Degradation of Mulit-Pass Transmembrane Protein

Cancer cells exploit proteins involved in energy metabolism to maintain a steady supply of building blocks necessary for increased proliferation. Many transporters play a role in the process of shuttling water, nutrients, ions, and various metabolic products across the cell membrane, including the solute carrier (SLC) group of proteins. The SLC protein group consists of more than 400 proteins organized into more than 50 families. For example, the SLC9 family is involved in intracellular pH homeostasis, with increased SL9 activity resulting in an elevated intracellular pH and cytosolic alkalinization in cancer. Currently there 12 FDA approved drugs targeting SLC proteins for conditions ranging from hypertension to depression, but recent studies suggest SLC proteins may be attractive targets for cancer drug development. With this end goal, Bensimon et al., aimed to investigate if multi-pass transmembrane proteins like SLCs can be chemically degraded. To first explore this aim, th...

Quantitative Chemical Biology

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