Immucillins in custom catalytic-site cavities.

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Murkin AS, Clinch K, Mason JM, Tyler PC, Schramm VL

Immucillins in custom catalytic-site cavities.

Bioorg Med Chem Lett. 2008 Nov 15;18(22):5900-3. doi: 10.1016/j.bmcl.2008.08.047. Epub 2008 Aug 19.

PubMed ID

18778937 [ View in PubMed

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Abstract

Neighboring-group participation in the reaction catalyzed by purine nucleoside phosphorylase involves a compression mode between the 5'- and 4'-ribosyl oxygens, facilitated by His257. The His257Gly mutant opens a space in the catalytic site. Hydrophobic 5'-substituted Immucillins are transition-state analogue inhibitors of this mutant enzyme. Dissociation constants as low as 2pM are achieved, with K(m)/K(d) as high as 400,000,000.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Forodesine	Purine nucleoside phosphorylase	Ki (nM)	3.3	N/A	N/A	Details
Forodesine	Purine nucleoside phosphorylase	Ki (nM)	0.0579	N/A	N/A	Details