RESUMO
The design, synthesis, and conformational analysis of a novel aromatic oligoester helix mimetic scaffold is reported. A range of amino acid-type side-chain functionality can be readily incorporated into monomer building blocks over three facile synthetic steps. Analysis of representative dimers revealed a stable conformer capable of effective mimicry of a canonical α-helix and the scaffold was found to be surprisingly stable to degradation in aqueous solutions at acidic and neutral pH.
Assuntos
Aminoácidos , Biomimética , Estrutura Secundária de ProteínaRESUMO
[This corrects the article DOI: 10.1039/D1MD00215E.].
RESUMO
Cooperativity is an important parameter to understand the ternary complexes formed by protein degraders. We developed fluorine NMR competition binding experiments to determine cooperativity of PROTACs. We show applicability to estimate both positive and negative cooperativity, also with homo-dimerizers, and highlight key features and considerations for optimal assay development.
RESUMO
Systematic characterization of a series of fluorinated VHL ligands, varying binding affinity and position of the trifluoromethyl group, qualifies a spy molecule for competitive 19F NMR screening and reveals guiding principles to develop highly sensitive assays with low material consumption.