article thumbnail

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.

article thumbnail

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.

article thumbnail

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.

article thumbnail

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.