Immucillins in custom catalytic-site cavities

Andrew S. Murkin, Keith Clinch, Jennifer M. Mason, Peter C. Tyler, Vern L. Schramm

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 2 pM are achieved, with Km/Kd as high as 400,000,000.

Original languageEnglish (US)
Pages (from-to)5900-5903
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume18
Issue number22
DOIs
StatePublished - Nov 15 2008

Fingerprint

Purine-Nucleoside Phosphorylase
Enzyme Inhibitors
Catalytic Domain
Oxygen
Enzymes

Keywords

  • Binding
  • ImmH
  • Immucillin
  • Mutant
  • PNP
  • Transition-state analogue

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

Immucillins in custom catalytic-site cavities. / Murkin, Andrew S.; Clinch, Keith; Mason, Jennifer M.; Tyler, Peter C.; Schramm, Vern L.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 18, No. 22, 15.11.2008, p. 5900-5903.

Research output: Contribution to journalArticle

Murkin, Andrew S. ; Clinch, Keith ; Mason, Jennifer M. ; Tyler, Peter C. ; Schramm, Vern L. / Immucillins in custom catalytic-site cavities. In: Bioorganic and Medicinal Chemistry Letters. 2008 ; Vol. 18, No. 22. pp. 5900-5903.
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