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Structure-Based Optimization of Covalent, Small-Molecule Stabilizers of the 14-3-3?/ER? Protein–Protein Interaction from Nonselective Fragments

Covalent Modifiers

Here, we show the structure-based optimization of the nonselective fragment toward selective and highly potent small-molecule stabilizers of the 14-3-3σ/ERα complex. Orthogonal biophysical assays, including mass spectrometry and fluorescence anisotropy, were used to establish structure–activity relationships.

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Location-agnostic site-specific protein bioconjugation via Baylis Hillman adducts

Covalent Modifiers

link] Proteins labelled site-specifically with small molecules are valuable assets for chemical biology and drug development. Nat Commun 15 , 859 (2024). The unique reactivity profile of the 1,2-aminothiol moiety of N -terminal cysteines ( N -Cys) of proteins renders it highly attractive for regioselective protein labelling.

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Biophysics

Sygnature Discovery

Comprehensive Assay Development for Diverse Applications Our team here at Sygnature Discovery, comprised of expert biophysicists, is highly experienced in a variety of target classes and drug modalities. Sygnature Discovery’s Biophysical Assay Development Capabilities: 1.

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Target-directed cancer: protein-ligand interactions  

Drug Target Review

The mission of the CCDD is to discover novel small-molecule therapeutics for the treatment of cancer and progress them to hypothesis testing phase 1 clinical trials. We have several exciting projects in various stages of discovery, but a small-molecule drug that is causing a lot of excitement at the moment is Capivasertib.