mRNA Display Identifies Potent, Paralog-Selective Peptidic Ligands for ARID1B.

The ARID1A and ARID1B subunits are mutually exclusive components of the BAF variant of SWI/SNF chromatin remodeling complexes. Loss of function mutations in ARID1A are frequently observed in various cancers, resulting in a dependency on the paralog ARID1B for cancer cell proliferation. However, ARID1B has never been targeted directly, and the high degree of sequence similarity to ARID1A poses a challenge for the development of selective binders.

Evolution of Novartis' Small Molecule Screening Deck Design.

This article summarizes the evolution of the screening deck at the Novartis Institutes for BioMedical Research (NIBR). Historically, the screening deck was an assembly of all available compounds. In 2015, we designed a first deck to facilitate access to diverse subsets with optimized properties.

Synthesis and structure of symmetrical bicyclic hexapeptides bridged by metathesis reaction.

[structure: see text] Bicyclic hexapeptides 1a-c were synthesized via an intramolecular ring-closing metathesis reaction on solid phase followed by an N- to C-terminal cyclization in solution. Structural elucidation showed that these compounds assumed a C2-symmetrical structure with two beta-turns. The trans-ethylene plane was found to occupy two positions in rapid interconversion.