Linked Life Data

18680270

Source:http://linkedlifedata.com/resource/pubmed/id/18680270

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2008-8-25
pubmed:abstractText
Pleuromutilin and its derivatives are antibacterial drugs that inhibit protein synthesis in bacteria by binding to ribosomes. To promote rational design of pleuromutilin based drugs, 19 pleuromutilin conjugates with different nucleoside fragments as side chain extensions were synthesized by a click chemistry protocol. Binding was assessed by chemical footprinting of nucleotide U2506 in 23S rRNA, and all conjugates bind to varying degree reflecting their binding affinity to the peptidyl transferase center. The side chain extensions also show various protections at position U2585. Docking studies of the conjugates with the highest affinities support the conclusion that despite the various conjugations, the pleuomutilin skeleton binds in the same binding pocket. The conjugated triazole moiety is well accommodated, and the nucleobases are placed in different pockets in the 50S ribosomal subunit. The derivative showing the highest affinity and a significantly better binding than pleuromutilin itself contains an adenine-9-ylpropylene triazole conjugate to pleuromutilin C-22.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1520-4804
pubmed:author
pubmed:issnType
Electronic
pubmed:day
28
pubmed:volume
51
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4957-67
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
A click chemistry approach to pleuromutilin conjugates with nucleosides or acyclic nucleoside derivatives and their binding to the bacterial ribosome.
pubmed:affiliation
Nucleic Acid Center, Department of Physics and Chemistry, University of Southern Denmark, 5230 Odense M, Denmark.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't