Discovery of Thioether-Cyclized Macrocyclic Covalent Inhibitors by mRNA Display.

Macrocyclic peptides are promising scaffolds for the covalent ligand discovery. However, platforms enabling the direct identification of covalent macrocyclic ligands in a high-throughput manner are limited. In this study, we present an mRNA display platform allowing selection of covalent macrocyclic inhibitors using 1,3-dibromoacetone-vinyl sulfone (DBA-VS).

Quantifying Amide-Aromatic Interactions at Molecular and Atomic Levels: Experimentally Determined Enthalpic and Entropic Contributions to Interactions of Amide spO, N, C and spC Unified Atoms with Naphthalene spC Atoms in Water.

In addition to amide hydrogen bonds and the hydrophobic effect, interactions involving π-bonded sp atoms of amides, aromatics, and other groups occur in protein self-assembly processes including folding, oligomerization, and condensate formation. These interactions also occur in aqueous solutions of amide and aromatic compounds, where they can be quantified. Previous analysis of thermodynamic coefficients quantifying net-favorable interactions of amide compounds with other amides and aromatics revealed that interactions of amide spO with amide spN unified atoms (presumably C═O···H-N hydrogen bonds) and amide/aromatic spC (lone pair π, n-π*) are particularly favorable.

Quantifying Amide-Aromatic Interactions at Molecular and Atomic Levels: Experimentally-determined Enthalpic and Entropic Contributions to Interactions of Amide sp O, N, C and sp C Unified Atoms with Naphthalene sp C Atoms in Water.

In addition to amide hydrogen bonds and the hydrophobic effect, interactions involving π-bonded sp atoms of amides, aromatics and other groups occur in protein self-assembly processes including folding, oligomerization and condensate formation. These interactions also occur in aqueous solutions of amide and aromatic compounds, where they can be quantified. Previous analysis of thermodynamic coefficients quantifying net-favorable interactions of amide compounds with other amides and aromatics revealed that interactions of amide sp O with amide sp N unified atoms (presumably C=O···H-N hydrogen bonds) and amide/aromatic sp C (lone pair-π, n-π ) are particularly favorable.