Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2003-11-17
pubmed:abstractText
Purine nucleoside phosphorylases (PNPs) catalyze nucleophilic displacement reactions by migration of the cationic ribooxacarbenium carbon between the fixed purine and phosphate nucleophiles. As the phosphorolysis reaction progresses along the reaction coordinate, the distance between the purine and carbocation increases and the distance between carbocation and phosphate anion decreases. Immucillin-H and Immucillin-G have been shown previously to be potent inhibitors of PNP. We now report the synthesis of a second generation of stable transition state analogues, DADMe-Immucillins 2, 3, and 4, with increased distance between ribooxacarbenium and purine mimics by incorporation of a methylene bridge between these groups. These compounds are potent inhibitors with equilibrium dissociation constants as low as 7 pM against human PNP. Stable chemical analogues of enzymatic transition states are necessarily imperfect since they lack the partial bond character of the transition state. The immucillins and DADMe-Immucillins represent approaches from the product and reaction side of the transition state.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5271-6
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Synthesis of second-generation transition state analogues of human purine nucleoside phosphorylase.
pubmed:affiliation
Carbohydrate Chemistry Team, Industrial Research Limited, PO Box 31310, Lower Hutt, New Zealand. g.evans@irl.cri.nz
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't