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https://hdl.handle.net/1959.11/8137
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DC Field | Value | Language |
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dc.contributor.author | Evans, Gary B | en |
dc.contributor.author | Furneaux, Richard H | en |
dc.contributor.author | Greatrex, Ben | en |
dc.contributor.author | Murkin, Andrew S | en |
dc.contributor.author | Schramm, Vern L | en |
dc.contributor.author | Tyler, Peter C | en |
dc.date.accessioned | 2011-07-22T12:45:00Z | - |
dc.date.issued | 2008 | - |
dc.identifier.citation | Journal of Medicinal Chemistry, 51(4), p. 948-956 | en |
dc.identifier.issn | 1520-4804 | en |
dc.identifier.issn | 0022-2623 | en |
dc.identifier.uri | https://hdl.handle.net/1959.11/8137 | - |
dc.description.abstract | N-Ribosyl phosphorylases and hydrolases catalyze nucleophilic displacement reactions by migration of the cationic ribooxacarbenium carbon from the fixed purine to phosphate and water nucleophiles, respectively. As the lysis reaction progresses along the reaction coordinate, the distance between the purine and carbocation increases and the distance between carbocation and nucleophile decreases. Immucillin-H and DADMe-immucillin-H have been shown previously to be potent inhibitors of purine nucleoside phosphorylases and lie more toward the reactant and products side of this reaction coordinate, respectively. Both these enzyme inhibitors, which are currently in human clinical trials for different indications, are chiral and expensive to manufacture. We now report the synthesis of azetidine analogues of the DADMe-immucillins, which, despite their lack of stereochemical complexity, remain potent inhibitors (equilibrium dissociation constants as low as 229 pM) of purine nucleoside phosphorylase (PNP), methylthioadenosine phosphorylase (MTAP), and methylthioadenosine nucleosidase (MTAN), with potential utility as drug candidates. | en |
dc.language | en | en |
dc.publisher | American Chemical Society | en |
dc.relation.ispartof | Journal of Medicinal Chemistry | en |
dc.title | Azetidine Based Transition State Analogue Inhibitors of N-Ribosyl Hydrolases and Phosphorylases | en |
dc.type | Journal Article | en |
dc.identifier.doi | 10.1021/jm701265n | en |
dc.subject.keywords | Organic Chemical Synthesis | en |
dc.subject.keywords | Biologically Active Molecules | en |
dc.subject.keywords | Enzymes | en |
local.contributor.firstname | Gary B | en |
local.contributor.firstname | Richard H | en |
local.contributor.firstname | Ben | en |
local.contributor.firstname | Andrew S | en |
local.contributor.firstname | Vern L | en |
local.contributor.firstname | Peter C | en |
local.subject.for2008 | 030503 Organic Chemical Synthesis | en |
local.subject.for2008 | 060107 Enzymes | en |
local.subject.for2008 | 030401 Biologically Active Molecules | en |
local.subject.seo2008 | 970106 Expanding Knowledge in the Biological Sciences | en |
local.subject.seo2008 | 970103 Expanding Knowledge in the Chemical Sciences | en |
local.subject.seo2008 | 920102 Cancer and Related Disorders | en |
local.profile.school | Science and Technology | en |
local.profile.school | Science and Technology | en |
local.profile.school | School of Rural Medicine | en |
local.profile.school | Science and Technology | en |
local.profile.school | Science and Technology | en |
local.profile.school | Science and Technology | en |
local.profile.email | g.evans@irl.cri.nz | en |
local.profile.email | r.furneaux@irl.cri.nz | en |
local.profile.email | bgreatre@une.edu.au | en |
local.profile.email | p.tyler@irl.cri.nz | en |
local.output.category | C1 | en |
local.record.place | au | en |
local.record.institution | University of New England | en |
local.identifier.epublicationsrecord | une-20110225-12460 | en |
local.publisher.place | United States of America | en |
local.format.startpage | 948 | en |
local.format.endpage | 956 | en |
local.identifier.scopusid | 39749114381 | en |
local.peerreviewed | Yes | en |
local.identifier.volume | 51 | en |
local.identifier.issue | 4 | en |
local.contributor.lastname | Evans | en |
local.contributor.lastname | Furneaux | en |
local.contributor.lastname | Greatrex | en |
local.contributor.lastname | Murkin | en |
local.contributor.lastname | Schramm | en |
local.contributor.lastname | Tyler | en |
dc.identifier.staff | une-id:bgreatre | en |
local.profile.orcid | 0000-0002-0356-4966 | en |
local.profile.role | author | en |
local.profile.role | author | en |
local.profile.role | author | en |
local.profile.role | author | en |
local.profile.role | author | en |
local.profile.role | author | en |
local.identifier.unepublicationid | une:8312 | en |
dc.identifier.academiclevel | Academic | en |
dc.identifier.academiclevel | Academic | en |
local.title.maintitle | Azetidine Based Transition State Analogue Inhibitors of N-Ribosyl Hydrolases and Phosphorylases | en |
local.output.categorydescription | C1 Refereed Article in a Scholarly Journal | en |
local.search.author | Evans, Gary B | en |
local.search.author | Furneaux, Richard H | en |
local.search.author | Greatrex, Ben | en |
local.search.author | Murkin, Andrew S | en |
local.search.author | Schramm, Vern L | en |
local.search.author | Tyler, Peter C | en |
local.uneassociation | Unknown | en |
local.year.published | 2008 | en |
Appears in Collections: | Journal Article School of Rural Medicine |
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