Inhibition of the Clathrin Terminal Domain-Amphiphysin Protein-Protein Interaction. Probing the Pitstop 2 Aromatic Moiety.

ABSTRACT: Pitstop 2, (Z)-N-(5-(4-bromenzylidene)-4-oxo-4,5-dihydrothiazol-2-yl)naphthalene-1-sulfonamide (1) inhibits the clathrin terminal domain-amphiphysin interaction (NTD-PPI) and has been widely used to investigate endocytosis. Herein, the synthesis of 56 novel Pitstop 2 analogues via four discrete focused libraries is reported. Specific modification to the 4-bromonenzylidene moiety is explored, and their ability to inhibit the NTD-PPI interaction is examined by ELISA. In cell endocytosis, effects are measured for selective analogues as is the inhibition of dynamin, another protein involved in the endocytosis process. The most NTD-PPI active analogues retain 2- and 4-disposed substituents on the aromatic head, with 2,3,4-trihydroxy (28) the most active (IC₅₀ 0.94 μm). Catechol-free

SUBMITTER: Prichard K 

PROVIDER: S-EPMC12368479 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature