Thermal stability of low molecular weight urokinase during heat treatment. II: Effect of polymeric additives
Turbidimetric or light scattering assays can be used to determine the extent of aggregation in protein formulations. Using low molecular weight urokinase (LMW-UK) as a model protein, the effect of polymeric additives on heat-induced aggregation was evaluated. Previous work has shown that under 60 de...
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| Veröffentlicht in: | Pharmaceutical research 1994-07, Vol.11 (7), p.1004-1008 |
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| creator | VRKLJAN, M FOSTER, T. M POWERS, M. E HENKIN, J PORTER, W. R STAACK, H CARPENTER, J. F MANNING, M. C |
| description | Turbidimetric or light scattering assays can be used to determine the extent of aggregation in protein formulations. Using low molecular weight urokinase (LMW-UK) as a model protein, the effect of polymeric additives on heat-induced aggregation was evaluated. Previous work has shown that under 60 degrees C heat treatment, LMW-UK initially denatures and the unfolded protein associates to form soluble aggregates. Eventually, these aggregates associate to form a precipitate. The effects of polymers on the initial aggregation phase was examined. Hydroxyethyl (heta) starch, polyethylene glycol 4000, and gelatin were found to be effective, concentration-dependent inhibitors of aggregation, whereas polyvinylpyrrolidone (PVP) and polyethylene glycol 300 were ineffective. Overall, the effect of polymeric additives on the stability of thermally-stressed LMW-UK can be accounted for by preferential exclusion of the solute from the surface of the protein. |
| doi_str_mv | 10.1023/a:1018935420680 |
| format | Article |
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II: Effect of polymeric additives</title><source>MEDLINE</source><source>SpringerLink Journals</source><creator>VRKLJAN, M ; FOSTER, T. M ; POWERS, M. E ; HENKIN, J ; PORTER, W. R ; STAACK, H ; CARPENTER, J. F ; MANNING, M. C</creator><creatorcontrib>VRKLJAN, M ; FOSTER, T. M ; POWERS, M. E ; HENKIN, J ; PORTER, W. R ; STAACK, H ; CARPENTER, J. F ; MANNING, M. C</creatorcontrib><description>Turbidimetric or light scattering assays can be used to determine the extent of aggregation in protein formulations. Using low molecular weight urokinase (LMW-UK) as a model protein, the effect of polymeric additives on heat-induced aggregation was evaluated. Previous work has shown that under 60 degrees C heat treatment, LMW-UK initially denatures and the unfolded protein associates to form soluble aggregates. Eventually, these aggregates associate to form a precipitate. The effects of polymers on the initial aggregation phase was examined. Hydroxyethyl (heta) starch, polyethylene glycol 4000, and gelatin were found to be effective, concentration-dependent inhibitors of aggregation, whereas polyvinylpyrrolidone (PVP) and polyethylene glycol 300 were ineffective. Overall, the effect of polymeric additives on the stability of thermally-stressed LMW-UK can be accounted for by preferential exclusion of the solute from the surface of the protein.</description><identifier>ISSN: 0724-8741</identifier><identifier>EISSN: 1573-904X</identifier><identifier>DOI: 10.1023/a:1018935420680</identifier><identifier>PMID: 7937540</identifier><identifier>CODEN: PHREEB</identifier><language>eng</language><publisher>New York, NY: Springer</publisher><subject>Biological and medical sciences ; Enzyme Stability ; General pharmacology ; Glycerol - pharmacology ; Hot Temperature ; Light ; Medical sciences ; Molecular Weight ; Nephelometry and Turbidimetry ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology. Drug treatments ; Polyethylene Glycols ; Polymers ; Povidone ; Protein Denaturation ; Protein Folding ; Scattering, Radiation ; Starch - pharmacology ; Urokinase-Type Plasminogen Activator - chemistry ; Urokinase-Type Plasminogen Activator - drug effects</subject><ispartof>Pharmaceutical research, 1994-07, Vol.11 (7), p.1004-1008</ispartof><rights>1994 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c262t-9caf87865e76cc1a5e0125dca94f8e29aa1002433683f62d981a4072b62d7a863</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4168980$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7937540$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>VRKLJAN, M</creatorcontrib><creatorcontrib>FOSTER, T. M</creatorcontrib><creatorcontrib>POWERS, M. E</creatorcontrib><creatorcontrib>HENKIN, J</creatorcontrib><creatorcontrib>PORTER, W. R</creatorcontrib><creatorcontrib>STAACK, H</creatorcontrib><creatorcontrib>CARPENTER, J. F</creatorcontrib><creatorcontrib>MANNING, M. C</creatorcontrib><title>Thermal stability of low molecular weight urokinase during heat treatment. II: Effect of polymeric additives</title><title>Pharmaceutical research</title><addtitle>Pharm Res</addtitle><description>Turbidimetric or light scattering assays can be used to determine the extent of aggregation in protein formulations. Using low molecular weight urokinase (LMW-UK) as a model protein, the effect of polymeric additives on heat-induced aggregation was evaluated. Previous work has shown that under 60 degrees C heat treatment, LMW-UK initially denatures and the unfolded protein associates to form soluble aggregates. Eventually, these aggregates associate to form a precipitate. The effects of polymers on the initial aggregation phase was examined. Hydroxyethyl (heta) starch, polyethylene glycol 4000, and gelatin were found to be effective, concentration-dependent inhibitors of aggregation, whereas polyvinylpyrrolidone (PVP) and polyethylene glycol 300 were ineffective. Overall, the effect of polymeric additives on the stability of thermally-stressed LMW-UK can be accounted for by preferential exclusion of the solute from the surface of the protein.</description><subject>Biological and medical sciences</subject><subject>Enzyme Stability</subject><subject>General pharmacology</subject><subject>Glycerol - pharmacology</subject><subject>Hot Temperature</subject><subject>Light</subject><subject>Medical sciences</subject><subject>Molecular Weight</subject><subject>Nephelometry and Turbidimetry</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology. Drug treatments</subject><subject>Polyethylene Glycols</subject><subject>Polymers</subject><subject>Povidone</subject><subject>Protein Denaturation</subject><subject>Protein Folding</subject><subject>Scattering, Radiation</subject><subject>Starch - pharmacology</subject><subject>Urokinase-Type Plasminogen Activator - chemistry</subject><subject>Urokinase-Type Plasminogen Activator - drug effects</subject><issn>0724-8741</issn><issn>1573-904X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kEtLAzEUhYMoWh9rV0IW4m40r8nDnUjVguBGwV25zdyx0cxMTTJK_70Vi5tzD5yPA_cQcsrZJWdCXsE1Z9w6WSvBtGU7ZMJrIyvH1OsumTAjVGWN4gfkMOd3xpjlTu2TfeOkqRWbkPi8xNRBpLnAIsRQ1nRoaRy-aTdE9GOERL8xvC0LHdPwEXrISJsxhf6NLhEKLWmjHfblks5m13TatujLb8dqiOsOU_AUmiaU8IX5mOy1EDOebO8RebmbPt8-VI9P97Pbm8fKCy1K5Ty01lhdo9Hec6iRcVE3HpxqLQoHwBkTSkptZatF4ywHtXl1sfEGrJZH5OKvd5WGzxFzmXche4wRehzGPDfaGGPlL3i2BcdFh818lUIHaT3fzrPJz7c5ZA-xTdD7kP8xxbV1lskf7Tx0cQ</recordid><startdate>199407</startdate><enddate>199407</enddate><creator>VRKLJAN, M</creator><creator>FOSTER, T. 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C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c262t-9caf87865e76cc1a5e0125dca94f8e29aa1002433683f62d981a4072b62d7a863</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>Biological and medical sciences</topic><topic>Enzyme Stability</topic><topic>General pharmacology</topic><topic>Glycerol - pharmacology</topic><topic>Hot Temperature</topic><topic>Light</topic><topic>Medical sciences</topic><topic>Molecular Weight</topic><topic>Nephelometry and Turbidimetry</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology. Drug treatments</topic><topic>Polyethylene Glycols</topic><topic>Polymers</topic><topic>Povidone</topic><topic>Protein Denaturation</topic><topic>Protein Folding</topic><topic>Scattering, Radiation</topic><topic>Starch - pharmacology</topic><topic>Urokinase-Type Plasminogen Activator - chemistry</topic><topic>Urokinase-Type Plasminogen Activator - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>VRKLJAN, M</creatorcontrib><creatorcontrib>FOSTER, T. M</creatorcontrib><creatorcontrib>POWERS, M. E</creatorcontrib><creatorcontrib>HENKIN, J</creatorcontrib><creatorcontrib>PORTER, W. R</creatorcontrib><creatorcontrib>STAACK, H</creatorcontrib><creatorcontrib>CARPENTER, J. F</creatorcontrib><creatorcontrib>MANNING, M. C</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Pharmaceutical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>VRKLJAN, M</au><au>FOSTER, T. M</au><au>POWERS, M. E</au><au>HENKIN, J</au><au>PORTER, W. R</au><au>STAACK, H</au><au>CARPENTER, J. F</au><au>MANNING, M. C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Thermal stability of low molecular weight urokinase during heat treatment. II: Effect of polymeric additives</atitle><jtitle>Pharmaceutical research</jtitle><addtitle>Pharm Res</addtitle><date>1994-07</date><risdate>1994</risdate><volume>11</volume><issue>7</issue><spage>1004</spage><epage>1008</epage><pages>1004-1008</pages><issn>0724-8741</issn><eissn>1573-904X</eissn><coden>PHREEB</coden><abstract>Turbidimetric or light scattering assays can be used to determine the extent of aggregation in protein formulations. Using low molecular weight urokinase (LMW-UK) as a model protein, the effect of polymeric additives on heat-induced aggregation was evaluated. Previous work has shown that under 60 degrees C heat treatment, LMW-UK initially denatures and the unfolded protein associates to form soluble aggregates. Eventually, these aggregates associate to form a precipitate. The effects of polymers on the initial aggregation phase was examined. Hydroxyethyl (heta) starch, polyethylene glycol 4000, and gelatin were found to be effective, concentration-dependent inhibitors of aggregation, whereas polyvinylpyrrolidone (PVP) and polyethylene glycol 300 were ineffective. Overall, the effect of polymeric additives on the stability of thermally-stressed LMW-UK can be accounted for by preferential exclusion of the solute from the surface of the protein.</abstract><cop>New York, NY</cop><pub>Springer</pub><pmid>7937540</pmid><doi>10.1023/a:1018935420680</doi><tpages>5</tpages></addata></record> |
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| identifier | ISSN: 0724-8741 |
| ispartof | Pharmaceutical research, 1994-07, Vol.11 (7), p.1004-1008 |
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| language | eng |
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| source | MEDLINE; SpringerLink Journals |
| subjects | Biological and medical sciences Enzyme Stability General pharmacology Glycerol - pharmacology Hot Temperature Light Medical sciences Molecular Weight Nephelometry and Turbidimetry Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments Polyethylene Glycols Polymers Povidone Protein Denaturation Protein Folding Scattering, Radiation Starch - pharmacology Urokinase-Type Plasminogen Activator - chemistry Urokinase-Type Plasminogen Activator - drug effects |
| title | Thermal stability of low molecular weight urokinase during heat treatment. II: Effect of polymeric additives |
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