Linked Life Data

9702213

Source:http://linkedlifedata.com/resource/pubmed/id/9702213

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1998-8-31
pubmed:abstractText
This paper reports an ongoing study of the use of small-ring-size cyclic peptides as carriers of a potential antitumor agent: 2,6-dimethoxyhydroquinone-3-mercaptoacetic acid (DMQ-MA). Three new cyclic tripeptide-DMQ-MA conjugates--cyclo[D-Val-Lys(DMQ-MA)-gamma-aminobutyric acid (GABA)-], cyclo[Val-Lys(DMQ-MA)-GABA-] and cyclo[D-Val-D-Lys(DMQ-MA)-GABA-]--were synthesized. The isomeric cyclic tripeptide-DMQ-MA conjugates were designed and synthesized to study the effect of stereoisomerism of the conjugates on cytotoxicity. The cyclic peptides were synthesized by coupling protected amino acids in solution and the final cyclization performed by the pentafluorophenyl ester method as described previously. After removing the lysyl-Z protecting group of the cyclic peptides the conjugation was achieved by reacting with the pentafluorophenyl ester of DMQ-MA. Electron spin resonance (ESR) studies of these three cyclic tripeptide-DMQ-MA conjugates showed that hydroxyl radicals were generated as a non-linear function of L-ascorbic acid (AH2) concentration. The IC50 of the cyclic tripeptide-DMQ-MA conjugates against a human pulmonary carcinoma cell line (PC-9 cells) under the synergistic activation of AH2 ranges from 0.4 to 1.6 microM, which is significantly lower than the parent compound DMQ-MA (6.1 microM). Agarose gel electrophoresis showed that DMQ-MA and these cyclic peptide-DMQ-MA conjugates are capable of cleaving supercoiled plasmid DNA to open circular and linear forms, even in the absence of AH2. The effects of enantiomeric and diastereomeric variations of these cyclic tripeptide-DMQ-MA conjugates on the cytotoxicity against PC-9 cells were discussed.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0266-9536
pubmed:author
pubmed:issnType
Print
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
501-18
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:9702213-Amino Acids, pubmed-meshheading:9702213-Antineoplastic Agents, pubmed-meshheading:9702213-Cell Survival, pubmed-meshheading:9702213-Chemistry, Physical, pubmed-meshheading:9702213-DNA, Neoplasm, pubmed-meshheading:9702213-Drug Screening Assays, Antitumor, pubmed-meshheading:9702213-Electron Spin Resonance Spectroscopy, pubmed-meshheading:9702213-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:9702213-Humans, pubmed-meshheading:9702213-Hydroquinones, pubmed-meshheading:9702213-Molecular Weight, pubmed-meshheading:9702213-Peptides, Cyclic, pubmed-meshheading:9702213-Physicochemical Phenomena, pubmed-meshheading:9702213-Spin Trapping, pubmed-meshheading:9702213-Stereoisomerism, pubmed-meshheading:9702213-Thioglycolates, pubmed-meshheading:9702213-Tumor Cells, Cultured
pubmed:year
1998
pubmed:articleTitle
Synthesis, DNA cleavage and cytotoxicity of some novel cyclic peptide-2,6-dimethoxyhydroquinone-3-mercaptoacetic acid conjugates containing D-amino acids.
pubmed:affiliation
Department of Chemistry, Tunghai Christian University, Taichung, Taiwan, ROC.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't