Linked Life Data

9020775

Source:http://linkedlifedata.com/resource/pubmed/id/9020775

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1997-3-13
pubmed:abstractText
CMP-ketodeoxyoctonate (CMP-KDO) and analogs, including CMP-5-deoxy-5-fluoro-KDO, CMP-5-deoxy-KDO, and CMP-5-epi-KDO, were prepared from CTP and the corresponding KDO sugars catalyzed by CMP-KDO synthetase. These analogs were found to be much more stable than CMP-KDO (t1/2 = 0.57 h) yet less stable than CMP-sialic acid (t1/2 = 151 h). Fluorination at the 5-position of CMP-KDO has a 200-fold enhanced stability compared to the 156-fold enhancement for the 3R-fluoro analog, probably due to the loss of H-bonding interactions (for the 5-F derivative) and the cause of remote inductive effect (for the 3- and the 5-F analogs) on the glycosidic cleavage. Hydrolysis of CMP-KDO is perhaps facilitated by an intramolecular hydrogen bond from the 5-OH group with the phosphate oxygen as demonstrated by the 3-5-fold enhanced stability of CMP-5-epi-KDO and CMP-5-deoxy-KDO compared to CMP-KDO and by molecular modeling studies of water-solvated CMP-KDO. Hydrolysis of CMP-KDO also was found to be subject to a substantial solvent isotope effect (kH/kD = 2.7), which is significantly different from the reported solvent isotope effect for the hydrolysis of sialyglycosides (kH/kD = 0.86) and dependent on both buffer and magnesium ion concentrations. Considering these results and molecular modeling studies, it is proposed that the hydrolysis of CMP-KDO under neutral conditions proceeds through a glycosidic cleavage which occurs at the electronically favorable twist-boat conformation, facilitated by intramolecular H-bonding interaction of the 4-, 5- and 7- (or 8-) OH groups and the phosphate oxygen and by the leaving group magnesium ion complexation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
28
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
780-5
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Why is CMP-ketodeoxyoctonate highly unstable?
pubmed:affiliation
Department of Chemistry, Scripps Research Institute, La Jolla, California 92037, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't