Linked Life Data

16351096

Source:http://linkedlifedata.com/resource/pubmed/id/16351096

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
50
pubmed:dateCreated
2005-12-14
pubmed:abstractText
The targeting of microtubules is an important mechanism for cancer chemotherapy. However, there is still a need for improved antimicrotubule agents. A number of seemingly structurally disparate peptidic natural products inhibit tubulin polymerization by binding to a region of the tubulin heterodimer close to the vinca binding site. An analogue of the naturally occurring tripeptide hemiasterlin, taltobulin (HTI-286, 3), has advanced to clinical trials. Structure-activity relationship studies of 3 have revealed critical structural elements necessary for antimicrotubule activity that correspond to comparable groups in the amino terminus tripeptide region of the dolastatins. To investigate the structural relationship between the hemiasterlins and the more complex dolastatins, hybrid compounds composed of 3 and the carboxy terminus dipeptides of dolastatin 10, or the dolastatin 15 analogue cemadotin, were synthesized. The resulting hybrid compounds were potent antimicrotubule agents, thus establishing a structural relationship between the hemiasterlins and the dolastatins. This relationship may be useful in the design of analogues having improved activity in resistant cell lines expressing the P-glycoprotein transporter, for establishing structural relationships with other classes of peptidic antimicrotubule agents, or for modeling studies of the tubulin binding site of these agents.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0002-7863
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
127
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
17667-71
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Hybrids of the hemiasterlin analogue taltobulin and the dolastatins are potent antimicrotubule agents.
pubmed:affiliation
Chemical and Screening Sciences and Oncology Research, Wyeth Research, 401 North Middletown Road, Pearl River, New York 10965, USA. zaska@wyeth.com
pubmed:publicationType
Journal Article