Immucillins in custom catalytic-site cavities

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

doi:10.1016/j.bmcl.2008.08.047

Immucillins in custom catalytic-site cavities

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

Biochemistry

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

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 K_m/K_d as high as 400,000,000.

Original language	English (US)
Pages (from-to)	5900-5903
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	18
Issue number	22
DOIs	https://doi.org/10.1016/j.bmcl.2008.08.047
State	Published - Nov 15 2008

Keywords

Binding
ImmH
Immucillin
Mutant
PNP
Transition-state analogue

ASJC Scopus subject areas

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

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10.1016/j.bmcl.2008.08.047

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title = "Immucillins in custom catalytic-site cavities",

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.",

keywords = "Binding, ImmH, Immucillin, Mutant, PNP, Transition-state analogue",

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T1 - Immucillins in custom catalytic-site cavities

AU - Murkin, Andrew S.

AU - Clinch, Keith

AU - Mason, Jennifer M.

AU - Tyler, Peter C.

AU - Schramm, Vern L.

PY - 2008/11/15

Y1 - 2008/11/15

N2 - 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.

AB - 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.

KW - Binding

KW - ImmH

KW - Immucillin

KW - Mutant

KW - PNP

KW - Transition-state analogue

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M3 - Article

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SN - 0960-894X

VL - 18

SP - 5900

EP - 5903

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 22

ER -

Immucillins in custom catalytic-site cavities

Abstract

Keywords

ASJC Scopus subject areas

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