Ontology type: schema:ScholarlyArticle
1984-10
AUTHORSL. Bielicki, G. Voelcker, H. J. Hohorst
ABSTRACTDNA polymerase I from E. coli can toxify activated cyclophosphamide (CP) by means of the 3'-5' exonuclease activity associated with the enzyme. Acrolein and an alkylating moiety are released in the process. Preincubation of DNA polymerase I with activated CP for 15-60 min leads to an increasing inhibition of DNA polymerase activity, which can be prevented when preincubation of DNA polymerase I with activated CP is carried out in the presence of 5' AMP, a competitive inhibitor of the 3'-5' exonuclease subsite of the enzyme. This demonstrates that toxification of activated CP by the 3'-5' exonuclease subsite of DNA polymerase is a prerequisite for the inhibition of DNA polymerase activity. The kinetics and the degree of DNA polymerase inhibition suggest that the alkylating moiety rather than acrolein released from activated CP during toxification is responsible for the inhibition of DNA polymerase. DNA polymerase with associated 3'-5' exonuclease activity has also been isolated from eukaryotic cells, and toxification of activated CP by such an enzyme (DNA polymerase delta from rabbit bone marrow) has been shown previously. Thus we suggest that toxification of activated CP by DNA polymerases/3'-5' exonucleases present mainly in proliferating cells might lead to the specific alkylation of macromolecules involved in the cell proliferation process, such as the DNA polymerase subsite of these enzymes and probably also the DNA bound to the enzymes. The relatively high cancerotoxic selectivity and cytotoxic specificity of activated CP could be based on this specific enzyme-mediated alkylation. More... »
PAGES195-198
http://scigraph.springernature.com/pub.10.1007/bf01032606
DOIhttp://dx.doi.org/10.1007/bf01032606
DIMENSIONShttps://app.dimensions.ai/details/publication/pub.1020291418
PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/6736107
JSON-LD is the canonical representation for SciGraph data.
TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT
[
{
"@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json",
"about": [
{
"id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0601",
"inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/",
"name": "Biochemistry and Cell Biology",
"type": "DefinedTerm"
},
{
"id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06",
"inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/",
"name": "Biological Sciences",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Acrolein",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Alkylation",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Animals",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Biotransformation",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Cyclophosphamide",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "DNA Polymerase I",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Exodeoxyribonuclease V",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Exodeoxyribonucleases",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Humans",
"type": "DefinedTerm"
}
],
"author": [
{
"affiliation": {
"name": [
"Zentrum der Biologischen Chemie der Johann Wolfgang Goethe-Universit\u00e4t, Theodor-Stern-Kai 7, D-6000, Frankfurt am Main 70, Federal Republic of Germany"
],
"type": "Organization"
},
"familyName": "Bielicki",
"givenName": "L.",
"id": "sg:person.01365215203.79",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01365215203.79"
],
"type": "Person"
},
{
"affiliation": {
"name": [
"Zentrum der Biologischen Chemie der Johann Wolfgang Goethe-Universit\u00e4t, Theodor-Stern-Kai 7, D-6000, Frankfurt am Main 70, Federal Republic of Germany"
],
"type": "Organization"
},
"familyName": "Voelcker",
"givenName": "G.",
"id": "sg:person.072236252.36",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.072236252.36"
],
"type": "Person"
},
{
"affiliation": {
"name": [
"Zentrum der Biologischen Chemie der Johann Wolfgang Goethe-Universit\u00e4t, Theodor-Stern-Kai 7, D-6000, Frankfurt am Main 70, Federal Republic of Germany"
],
"type": "Organization"
},
"familyName": "Hohorst",
"givenName": "H. J.",
"id": "sg:person.053543626.71",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.053543626.71"
],
"type": "Person"
}
],
"citation": [
{
"id": "https://doi.org/10.1016/s0079-6603(08)60396-7",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1007749632"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/0006-2952(74)90318-9",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1013048117"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/0006-2952(74)90318-9",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1013048117"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1007/bf00284124",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1013128331",
"https://doi.org/10.1007/bf00284124"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1007/bf00405956",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1043928656",
"https://doi.org/10.1007/bf00405956"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1007/bf00405956",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1043928656",
"https://doi.org/10.1007/bf00405956"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1007/bf00262420",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1049693978",
"https://doi.org/10.1007/bf00262420"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1007/bf00262420",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1049693978",
"https://doi.org/10.1007/bf00262420"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1007/bf00391828",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1052681528",
"https://doi.org/10.1007/bf00391828"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1007/bf00391828",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1052681528",
"https://doi.org/10.1007/bf00391828"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1021/bi00577a034",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1055181407"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1021/bi00636a002",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1055183525"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1021/bi00658a018",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1055184304"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1126/science.185.4148.320",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1062510041"
],
"type": "CreativeWork"
},
{
"id": "https://app.dimensions.ai/details/publication/pub.1075292457",
"type": "CreativeWork"
},
{
"id": "https://app.dimensions.ai/details/publication/pub.1075292477",
"type": "CreativeWork"
},
{
"id": "https://app.dimensions.ai/details/publication/pub.1075794395",
"type": "CreativeWork"
},
{
"id": "https://app.dimensions.ai/details/publication/pub.1080283389",
"type": "CreativeWork"
},
{
"id": "https://app.dimensions.ai/details/publication/pub.1080747541",
"type": "CreativeWork"
},
{
"id": "https://app.dimensions.ai/details/publication/pub.1082128901",
"type": "CreativeWork"
}
],
"datePublished": "1984-10",
"datePublishedReg": "1984-10-01",
"description": "DNA polymerase I from E. coli can toxify activated cyclophosphamide (CP) by means of the 3'-5' exonuclease activity associated with the enzyme. Acrolein and an alkylating moiety are released in the process. Preincubation of DNA polymerase I with activated CP for 15-60 min leads to an increasing inhibition of DNA polymerase activity, which can be prevented when preincubation of DNA polymerase I with activated CP is carried out in the presence of 5' AMP, a competitive inhibitor of the 3'-5' exonuclease subsite of the enzyme. This demonstrates that toxification of activated CP by the 3'-5' exonuclease subsite of DNA polymerase is a prerequisite for the inhibition of DNA polymerase activity. The kinetics and the degree of DNA polymerase inhibition suggest that the alkylating moiety rather than acrolein released from activated CP during toxification is responsible for the inhibition of DNA polymerase. DNA polymerase with associated 3'-5' exonuclease activity has also been isolated from eukaryotic cells, and toxification of activated CP by such an enzyme (DNA polymerase delta from rabbit bone marrow) has been shown previously. Thus we suggest that toxification of activated CP by DNA polymerases/3'-5' exonucleases present mainly in proliferating cells might lead to the specific alkylation of macromolecules involved in the cell proliferation process, such as the DNA polymerase subsite of these enzymes and probably also the DNA bound to the enzymes. The relatively high cancerotoxic selectivity and cytotoxic specificity of activated CP could be based on this specific enzyme-mediated alkylation.",
"genre": "research_article",
"id": "sg:pub.10.1007/bf01032606",
"inLanguage": [
"en"
],
"isAccessibleForFree": false,
"isPartOf": [
{
"id": "sg:journal.1313647",
"issn": [
"0171-5216",
"1432-1335"
],
"name": "Journal of Cancer Research and Clinical Oncology",
"type": "Periodical"
},
{
"issueNumber": "3",
"type": "PublicationIssue"
},
{
"type": "PublicationVolume",
"volumeNumber": "107"
}
],
"name": "Activated cyclophosphamide: An enzyme-mechanism-based suicide inactivator of DNA polymerase/3\u2032\u20135\u2032 exonuclease",
"pagination": "195-198",
"productId": [
{
"name": "readcube_id",
"type": "PropertyValue",
"value": [
"60af04065009ce9f51ccea3fbd930bcf3f79348bcffbdf83af9c681f01777a4d"
]
},
{
"name": "pubmed_id",
"type": "PropertyValue",
"value": [
"6736107"
]
},
{
"name": "nlm_unique_id",
"type": "PropertyValue",
"value": [
"7902060"
]
},
{
"name": "doi",
"type": "PropertyValue",
"value": [
"10.1007/bf01032606"
]
},
{
"name": "dimensions_id",
"type": "PropertyValue",
"value": [
"pub.1020291418"
]
}
],
"sameAs": [
"https://doi.org/10.1007/bf01032606",
"https://app.dimensions.ai/details/publication/pub.1020291418"
],
"sdDataset": "articles",
"sdDatePublished": "2019-04-10T13:08",
"sdLicense": "https://scigraph.springernature.com/explorer/license/",
"sdPublisher": {
"name": "Springer Nature - SN SciGraph project",
"type": "Organization"
},
"sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000001_0000000264/records_8659_00000487.jsonl",
"type": "ScholarlyArticle",
"url": "http://link.springer.com/10.1007/BF01032606"
}
]Download the RDF metadata as: json-ld nt turtle xml License info
JSON-LD is a popular format for linked data which is fully compatible with JSON.
curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1007/bf01032606'
N-Triples is a line-based linked data format ideal for batch operations.
curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1007/bf01032606'
Turtle is a human-readable linked data format.
curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/bf01032606'
RDF/XML is a standard XML format for linked data.
curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/bf01032606'
This table displays all metadata directly associated to this object as RDF triples.
168 TRIPLES
21 PREDICATES
54 URIs
30 LITERALS
18 BLANK NODES