Build-Couple-Transform: A Paradigm for Lead-like Library Synthesis with Scaffold Diversity.

High-throughput screening provides one of the most common ways of finding hit compounds. Lead-like libraries, in particular, provide hits with compatible functional groups and vectors for structural elaboration and physical properties suitable for optimization. Library synthesis approaches can lead to a lack of chemical diversity because they employ parallel derivatization of common building blocks using single reaction types.

Functional Group Tolerance of a Micellar on-DNA Suzuki-Miyaura Cross-Coupling Reaction for DNA-Encoded Library Design.

DNA-encoded libraries (DELs) offer great promise for the discovery of new ligands for proteins. Many current reactions used for DEL synthesis do not proceed efficiently over a wide range of substrates. Combining a diverse array of multicomponent reactions with micellar-promoted Suzuki-Miyaura cross-coupling provides a strategy for synthesizing highly diverse DELs with exceptionally high fidelity.

Micellar Buchwald-Hartwig Coupling of Aryl and Heteroarylamines for the Synthesis of DNA-Encoded Libraries.

DNA-encoded libraries are a very efficient means of identifying ligands for protein targets in high throughput. To fully maximize their use, it is essential to be able to carry out efficient reactions on DNA-conjugated substrates. Arylamines are privileged motifs in druglike molecules, and methods for their incorporation into DNA-encoded libraries are highly desirable.

Highly efficient on-DNA amide couplings promoted by micelle forming surfactants for the synthesis of DNA encoded libraries.

DNA encoded libraries (DELs) represent powerful new technology for finding small molecule ligands for proteins and are increasingly being applied to hit finding in medicinal chemistry. Crucial to the synthesis of high quality DELs is the identification of chemical reactions for their assembly that proceed with very high conversion across a range of different substrates, under conditions compatible with DNA-tagged substrates. Many current chemistries used in DEL synthesis do not meet this requirement, resulting in libraries of low fidelity.

The maturation of DNA encoded libraries: opportunities for new users.

DNA-encoded combinatorial libraries (DECLs) represent an exciting new technology for high-throughput screening, significantly increasing its capacity and cost-effectiveness. Historically, DECLs have been the domain of specialized academic groups and industry; however, there has recently been a shift toward more drug discovery academic centers and institutes adopting this technology. Key to this development has been the simplification, characterization and standardization of various DECL subprotocols, such as library design, affinity screening and data analysis of hits.

High Fidelity Suzuki-Miyaura Coupling for the Synthesis of DNA Encoded Libraries Enabled by Micelle Forming Surfactants.

DNA encoded chemical libraries provide a highly efficient means of screening vast numbers of small molecules against an immobilized protein target. Their potential is currently restricted by the constraints of carrying out library synthesis in the presence of attached DNA tags, for which a limited number of reactions and substrates can be used. Even established reactions, such as Suzuki-Miyaura couplings, do not give efficient coupling reactions across a wide range of substrates and can lead to significant DNA degradation.

Self-gravity driven instabilities at accelerated interfaces.

Nonlinear hydrodynamic flows are ubiquitous in the interstellar medium (ISM). Such flows play an important role in shaping atomic and molecular clouds and determining the initial conditions for star formation. One mechanism by which nonlinear flows arise is the onset and growth of interfacial instabilities.