Dynamic Combinatorial Chemistry: Lysozyme Selects an Aromatic Motif That Mimics a Carbohydrate Residue

Abstract

Lysozym trifft seine Wahl: Hühnereiweiß‐Lysozym wählt aus einer Sammlung von aromatischen Motiven, die eine Kohlenhydrateinheit nachahmen, den optimalen Bindungspartner aus, wenn es einer dynamischen Bibliothek potenzieller Liganden ausgesetzt wird, die durch ein niedrigaffines Gerüst auf sein aktives Zentrum gelenkt werden. Die Struktur einer der gewählten Verbindungen ist gezeigt (1).

Bivalent Enzyme Inhibitors Discovered Using Dynamic Covalent Chemistry

“…Pioneering work in biological DCC has featured protein targets that were necessarily well understood in terms of medicinal chemistry structure-activity relationships (SAR), with DCLs producing hit structures largely comprising known binding motifs. [4] This was required to correlate the observed behaviour of DCLs in terms of amplifications with binding affinities. The future development of protein-directed DCC will depend on exploiting its complementarity to conventional methods, [5] and applying it to targets that would challenge standard drug discovery approaches.…”

Exploiting Neighboring‐Group Interactions for the Self‐Selection of a Catalytic Unit

“…Such a covalent post-modification is very common in imine-based dynamic combinatorial chemistry. [18] Secondly, the resulting secondary amine had to be methylated to prevent an intramolecular attack of the amine on the neighboring ester.…”