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.

Design, Synthesis, and Biological Evaluation of Chemically and Biologically Diverse Pyrroquinoline Pseudo Natural Products.

Natural product (NP) structures are a rich source of inspiration for the discovery of new biologically relevant chemical matter. In natural product inspired pseudo-NPs, NP-derived fragments are combined de novo in unprecedented arrangements. Described here is the design and synthesis of a 155-member pyrroquinoline pseudo-NP collection in which fragments characteristic of the tetrahydroquinoline and pyrrolidine NP classes are combined with eight different connectivities and regioisomeric arrangements.

Guided by evolution: from biology oriented synthesis to pseudo natural products.

Covering: up to 2020 Natural products (NPs) provide inspiration for the design of biologically active compounds and libraries. In this review, we cover several experimental and in silico approaches, which have been used to simplify NPs and guide NP-based library design. Earlier approaches, like the structural classification of natural products (SCONP) and biology-oriented synthesis (BIOS), focus on the identification of activity determining scaffolds and the synthesis of corresponding compound collections.

A Modular Synthesis of Modified Phosphoanhydrides.

Phosphoanhydrides (P-anhydrides) are ubiquitously occurring modifications in nature. Nucleotides and their conjugates, for example, are among the most important building blocks and signaling molecules in cell biology. To study and manipulate their biological functions, a diverse range of analogues have been developed.

Iterative synthesis of nucleoside oligophosphates with phosphoramidites.

P-Amidites can be used in iterative couplings to selectively give mixed P(III) -P(V) anhydrides. These intermediates can be oxidized followed by a rapid removal of the two terminal fluorenylmethyl groups. An iterative synthesis (coupling, oxidation, deprotection) of nucleoside oligophosphates can be carried out in solution and on a solid support.