868140-84-5Relevant articles and documents
Rational design, synthesis, and characterization of novel inhibitors for human β1,4-galactosyltransferase
Takaya, Kenji,Nagahori, Noriko,Kurogochi, Masaki,Furuike, Tetsuya,Miura, Nobuaki,Monde, Kenji,Lee, Yuan Chuan,Nishimura, Shin-Ichiro
, p. 6054 - 6065 (2007/10/03)
An affinity labeling reagent, uridine 5′-(6-amino-{2-[(7-bromomethyl- 2-naphthyl)methoxycarbonylmethoxy]ethoxy}acetyl-6-deoxy-α-D- galactopyranosyl) diphosphate (1a), was designed on the basis of 3D docking simulation and synthesized to investigate the functional role of Trp310 residue located in the small loop near the active site of human recombinant galactosyltransferase (βGalT-1). Mass spectrometric analysis revealed that the Trp310 residue of βGalT1 can be selectively modified with the naphthylmethyl group of compound 1a at the C-3 position of the indole ring. This result motivated us to synthesize novel uridine-5′-diphosphogalactose (UDP-Gal) analogues as candidates for mechanism-based inhibitors for βGalT-1. We found that uridine 5′-(6-O-[10-(2-naphthyl)-3,6,9- trioxadecanyl]-α-D-galactopyranosyl) diphosphate (2) is the strongest inhibitor (Ki = 1.86 μM) against UDP-Gal (Km, = 4.91 μM) among compounds reported previously. A cold spray ionization time-of-flight mass spectrometry study demonstrated that the complex of this inhibitor and βGalT-1 cannot interact with an acceptor substrate in the presence of Mn2+.
