Source:http://linkedlifedata.com/resource/pubmed/id/11478876
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
31
|
| pubmed:dateCreated |
2001-7-31
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| pubmed:abstractText |
Onconase, a member of the RNase A superfamily, is a potent antitumor agent which is undergoing phase III clinical trials as an antitumor drug. We have recently shown that onconase is an unusually stable protein. Furthermore, the protein is resistant to the action of proteases, which could influence its use as a drug, prolonging its biological life, and leading to its renal toxicity. Our investigation focused on the contribution of chain termini to onconase conformational stability and biological activities. We used differential scanning calorimetry, isothermal unfolding experiments, limited proteolysis, and catalytic and antitumor activity determinations to investigate the effect of the elimination of the two blocks at the chain termini, the N-terminal cyclized glutamine and the C-terminal disulfide bridge between the terminal Cys104 and Cys87. The determination of the thermodynamic parameters of the protein led to the conclusion that the two blocks at onconase chain termini are responsible for the unusual stability of the protein. Moreover, the reduced stability of the onconase mutants does not influence greatly their catalytic and antitumor activities. Thus, our data would suggest that an onconase-based drug, with a decreased toxicity, could be obtained through the use of less stable onconase variants.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Guanidine,
http://linkedlifedata.com/resource/pubmed/chemical/Pepsin A,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ribonucleases,
http://linkedlifedata.com/resource/pubmed/chemical/ranpirnase
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| pubmed:status |
MEDLINE
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| pubmed:month |
Aug
|
| pubmed:issn |
0006-2960
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
7
|
| pubmed:volume |
40
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
9097-103
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:11478876-3T3 Cells,
pubmed-meshheading:11478876-Animals,
pubmed-meshheading:11478876-Antineoplastic Agents,
pubmed-meshheading:11478876-Calorimetry, Differential Scanning,
pubmed-meshheading:11478876-Catalysis,
pubmed-meshheading:11478876-Cell Line, Transformed,
pubmed-meshheading:11478876-Guanidine,
pubmed-meshheading:11478876-Hot Temperature,
pubmed-meshheading:11478876-Humans,
pubmed-meshheading:11478876-Hydrolysis,
pubmed-meshheading:11478876-K562 Cells,
pubmed-meshheading:11478876-Mice,
pubmed-meshheading:11478876-Mice, Inbred BALB C,
pubmed-meshheading:11478876-Mutagenesis, Site-Directed,
pubmed-meshheading:11478876-Pepsin A,
pubmed-meshheading:11478876-Peptide Fragments,
pubmed-meshheading:11478876-Protein Conformation,
pubmed-meshheading:11478876-Protein Denaturation,
pubmed-meshheading:11478876-Rana pipiens,
pubmed-meshheading:11478876-Recombinant Proteins,
pubmed-meshheading:11478876-Ribonucleases
|
| pubmed:year |
2001
|
| pubmed:articleTitle |
Contribution of chain termini to the conformational stability and biological activity of onconase.
|
| pubmed:affiliation |
Dipartimento di Chimica Biologica, Università di Napoli Federico II, Via Mezzocannone, 16-80134 Napoli, Italy.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|