A carbohydrate-antioxidant hybrid polymer reduces oxidative damage in spermatozoa and enhances fertility
Gamete-gamete interactions are critically modulated by carbohydrate-protein interactions that rely on the carbohydrate-selective recognition of polyvalent carbohydrate structures 1 , 2 . A galactose-binding protein has been identified in mammalian spermatozoa 3 that has similarity to the well-charac...
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| Veröffentlicht in: | Nature chemical biology 2005-10, Vol.1 (5), p.270-274 |
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| creator | Fleming, Craig Maldjian, André Da Costa, Daniel Rullay, Attvinder K Haddleton, David M St John, Justin Penny, Paul Noble, Raymond C Cameron, Neil R Davis, Benjamin G |
| description | Gamete-gamete interactions are critically modulated by carbohydrate-protein interactions that rely on the carbohydrate-selective recognition of polyvalent carbohydrate structures
1
,
2
. A galactose-binding protein has been identified in mammalian spermatozoa
3
that has similarity to the well-characterized hepatic asialoglycoprotein receptor
4
. With the aim of exploiting the ability of this class of proteins to bind and internalize macromolecules displaying galactose, we designed hybrid carbohydrate-antioxidant polymers to deliver antioxidant vitamin E (α-tocopherol) to porcine spermatozoa. Treatment of sperm cells with one hybrid polymer in particular produced large increases in intracellular sperm levels of α-tocopherol and greatly reduced endogenous fatty acid degradation under oxidative stress. The polymer-treated spermatozoa had enhanced physiological properties and longer half-lives, which resulted in enhanced fertilization rates. Our results indicate that hybrid polymer delivery systems can prolong the functional viability of mammalian spermatozoa and improve fertility rates, and that our functionally guided optimization strategy can be applied to the discovery of active glycoconjugate ligands. |
| doi_str_mv | 10.1038/nchembio730 |
| format | Article |
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1
,
2
. A galactose-binding protein has been identified in mammalian spermatozoa
3
that has similarity to the well-characterized hepatic asialoglycoprotein receptor
4
. With the aim of exploiting the ability of this class of proteins to bind and internalize macromolecules displaying galactose, we designed hybrid carbohydrate-antioxidant polymers to deliver antioxidant vitamin E (α-tocopherol) to porcine spermatozoa. Treatment of sperm cells with one hybrid polymer in particular produced large increases in intracellular sperm levels of α-tocopherol and greatly reduced endogenous fatty acid degradation under oxidative stress. The polymer-treated spermatozoa had enhanced physiological properties and longer half-lives, which resulted in enhanced fertilization rates. Our results indicate that hybrid polymer delivery systems can prolong the functional viability of mammalian spermatozoa and improve fertility rates, and that our functionally guided optimization strategy can be applied to the discovery of active glycoconjugate ligands.</description><identifier>ISSN: 1552-4450</identifier><identifier>EISSN: 1552-4469</identifier><identifier>DOI: 10.1038/nchembio730</identifier><identifier>PMID: 16408056</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>alpha-Tocopherol - chemistry ; alpha-Tocopherol - pharmacology ; Animals ; Antioxidants ; Antioxidants - chemical synthesis ; Antioxidants - pharmacology ; Biochemical Engineering ; Biochemistry ; Bioorganic Chemistry ; Cell Biology ; Cell Survival - drug effects ; Chemistry ; Chemistry/Food Science ; Fatty acids ; Fertility ; Fertility - drug effects ; Fertility - physiology ; Fertility Agents, Male - chemical synthesis ; Fertility Agents, Male - pharmacology ; Glycoconjugates - chemical synthesis ; Glycoconjugates - pharmacology ; Humans ; letter ; Male ; Mammals ; Microscopy, Fluorescence ; Models, Biological ; Molecular Structure ; Oxidative stress ; Physiology ; Polymers ; Polymers - chemical synthesis ; Polymers - metabolism ; Polymers - pharmacology ; Sperm Motility - drug effects ; Spermatozoa - chemistry ; Spermatozoa - drug effects ; Spermatozoa - ultrastructure ; Swine</subject><ispartof>Nature chemical biology, 2005-10, Vol.1 (5), p.270-274</ispartof><rights>Springer Nature America, Inc. 2005</rights><rights>Copyright Nature Publishing Group Oct 2005</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c351t-50399ecc65cf7c56622053090512ff53e046f2b57740da85c5efefad6108531b3</citedby><cites>FETCH-LOGICAL-c351t-50399ecc65cf7c56622053090512ff53e046f2b57740da85c5efefad6108531b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/nchembio730$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/nchembio730$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51297</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16408056$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fleming, Craig</creatorcontrib><creatorcontrib>Maldjian, André</creatorcontrib><creatorcontrib>Da Costa, Daniel</creatorcontrib><creatorcontrib>Rullay, Attvinder K</creatorcontrib><creatorcontrib>Haddleton, David M</creatorcontrib><creatorcontrib>St John, Justin</creatorcontrib><creatorcontrib>Penny, Paul</creatorcontrib><creatorcontrib>Noble, Raymond C</creatorcontrib><creatorcontrib>Cameron, Neil R</creatorcontrib><creatorcontrib>Davis, Benjamin G</creatorcontrib><title>A carbohydrate-antioxidant hybrid polymer reduces oxidative damage in spermatozoa and enhances fertility</title><title>Nature chemical biology</title><addtitle>Nat Chem Biol</addtitle><addtitle>Nat Chem Biol</addtitle><description>Gamete-gamete interactions are critically modulated by carbohydrate-protein interactions that rely on the carbohydrate-selective recognition of polyvalent carbohydrate structures
1
,
2
. A galactose-binding protein has been identified in mammalian spermatozoa
3
that has similarity to the well-characterized hepatic asialoglycoprotein receptor
4
. With the aim of exploiting the ability of this class of proteins to bind and internalize macromolecules displaying galactose, we designed hybrid carbohydrate-antioxidant polymers to deliver antioxidant vitamin E (α-tocopherol) to porcine spermatozoa. Treatment of sperm cells with one hybrid polymer in particular produced large increases in intracellular sperm levels of α-tocopherol and greatly reduced endogenous fatty acid degradation under oxidative stress. The polymer-treated spermatozoa had enhanced physiological properties and longer half-lives, which resulted in enhanced fertilization rates. Our results indicate that hybrid polymer delivery systems can prolong the functional viability of mammalian spermatozoa and improve fertility rates, and that our functionally guided optimization strategy can be applied to the discovery of active glycoconjugate ligands.</description><subject>alpha-Tocopherol - chemistry</subject><subject>alpha-Tocopherol - pharmacology</subject><subject>Animals</subject><subject>Antioxidants</subject><subject>Antioxidants - chemical synthesis</subject><subject>Antioxidants - pharmacology</subject><subject>Biochemical Engineering</subject><subject>Biochemistry</subject><subject>Bioorganic Chemistry</subject><subject>Cell Biology</subject><subject>Cell Survival - drug effects</subject><subject>Chemistry</subject><subject>Chemistry/Food Science</subject><subject>Fatty acids</subject><subject>Fertility</subject><subject>Fertility - drug effects</subject><subject>Fertility - physiology</subject><subject>Fertility Agents, Male - chemical synthesis</subject><subject>Fertility Agents, Male - pharmacology</subject><subject>Glycoconjugates - chemical synthesis</subject><subject>Glycoconjugates - pharmacology</subject><subject>Humans</subject><subject>letter</subject><subject>Male</subject><subject>Mammals</subject><subject>Microscopy, Fluorescence</subject><subject>Models, Biological</subject><subject>Molecular Structure</subject><subject>Oxidative stress</subject><subject>Physiology</subject><subject>Polymers</subject><subject>Polymers - chemical synthesis</subject><subject>Polymers - metabolism</subject><subject>Polymers - pharmacology</subject><subject>Sperm Motility - drug effects</subject><subject>Spermatozoa - chemistry</subject><subject>Spermatozoa - drug effects</subject><subject>Spermatozoa - ultrastructure</subject><subject>Swine</subject><issn>1552-4450</issn><issn>1552-4469</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpt0MFL3zAUB_AwHNM5T7uP4GEX1-0ladL2KDI3QdjFnUuavNhIm_yWtGL9663-fugQT-_B-_BN-BLymcF3BqL-EUyPY-djJeAdOWBS8qIsVbP3vEvYJx9zvgEQSrH6A9lnqoQapDog_Sk1OnWxX2zSExY6TD7eebtO2i9d8pZu4rCMmGhCOxvM9Ok8-VukVo_6GqkPNG8wjXqK91FTHSzF0OvwiB2myQ9-Wj6R904PGY9285D8Pf95dfa7uPzz6-Ls9LIwQrKpkCCaBo1R0rjKSKU4BymgAcm4c1IglMrxTlZVCVbX0kh06LRVDGopWCcOyddt7ibFfzPmqR19NjgMOmCcc6saUKXiYoXHr-BNnFNY_9ZyzivRSF6v6GSLTIo5J3TtJvlRp6Vl0D623_7X_qq_7CLnbkT7Ynd1r-DbFuT1FK4xvbz5Vt4D_mySEQ</recordid><startdate>20051001</startdate><enddate>20051001</enddate><creator>Fleming, Craig</creator><creator>Maldjian, André</creator><creator>Da Costa, Daniel</creator><creator>Rullay, Attvinder K</creator><creator>Haddleton, David M</creator><creator>St John, Justin</creator><creator>Penny, Paul</creator><creator>Noble, Raymond C</creator><creator>Cameron, Neil R</creator><creator>Davis, Benjamin G</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PCBAR</scope><scope>PDBOC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20051001</creationdate><title>A carbohydrate-antioxidant hybrid polymer reduces oxidative damage in spermatozoa and enhances fertility</title><author>Fleming, Craig ; Maldjian, André ; Da Costa, Daniel ; Rullay, Attvinder K ; Haddleton, David M ; St John, Justin ; Penny, Paul ; Noble, Raymond C ; Cameron, Neil R ; Davis, Benjamin G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c351t-50399ecc65cf7c56622053090512ff53e046f2b57740da85c5efefad6108531b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>alpha-Tocopherol - 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Academic</collection><jtitle>Nature chemical biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fleming, Craig</au><au>Maldjian, André</au><au>Da Costa, Daniel</au><au>Rullay, Attvinder K</au><au>Haddleton, David M</au><au>St John, Justin</au><au>Penny, Paul</au><au>Noble, Raymond C</au><au>Cameron, Neil R</au><au>Davis, Benjamin G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A carbohydrate-antioxidant hybrid polymer reduces oxidative damage in spermatozoa and enhances fertility</atitle><jtitle>Nature chemical biology</jtitle><stitle>Nat Chem Biol</stitle><addtitle>Nat Chem Biol</addtitle><date>2005-10-01</date><risdate>2005</risdate><volume>1</volume><issue>5</issue><spage>270</spage><epage>274</epage><pages>270-274</pages><issn>1552-4450</issn><eissn>1552-4469</eissn><abstract>Gamete-gamete interactions are critically modulated by carbohydrate-protein interactions that rely on the carbohydrate-selective recognition of polyvalent carbohydrate structures
1
,
2
. A galactose-binding protein has been identified in mammalian spermatozoa
3
that has similarity to the well-characterized hepatic asialoglycoprotein receptor
4
. With the aim of exploiting the ability of this class of proteins to bind and internalize macromolecules displaying galactose, we designed hybrid carbohydrate-antioxidant polymers to deliver antioxidant vitamin E (α-tocopherol) to porcine spermatozoa. Treatment of sperm cells with one hybrid polymer in particular produced large increases in intracellular sperm levels of α-tocopherol and greatly reduced endogenous fatty acid degradation under oxidative stress. The polymer-treated spermatozoa had enhanced physiological properties and longer half-lives, which resulted in enhanced fertilization rates. Our results indicate that hybrid polymer delivery systems can prolong the functional viability of mammalian spermatozoa and improve fertility rates, and that our functionally guided optimization strategy can be applied to the discovery of active glycoconjugate ligands.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>16408056</pmid><doi>10.1038/nchembio730</doi><tpages>5</tpages></addata></record> |
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| subjects | alpha-Tocopherol - chemistry alpha-Tocopherol - pharmacology Animals Antioxidants Antioxidants - chemical synthesis Antioxidants - pharmacology Biochemical Engineering Biochemistry Bioorganic Chemistry Cell Biology Cell Survival - drug effects Chemistry Chemistry/Food Science Fatty acids Fertility Fertility - drug effects Fertility - physiology Fertility Agents, Male - chemical synthesis Fertility Agents, Male - pharmacology Glycoconjugates - chemical synthesis Glycoconjugates - pharmacology Humans letter Male Mammals Microscopy, Fluorescence Models, Biological Molecular Structure Oxidative stress Physiology Polymers Polymers - chemical synthesis Polymers - metabolism Polymers - pharmacology Sperm Motility - drug effects Spermatozoa - chemistry Spermatozoa - drug effects Spermatozoa - ultrastructure Swine |
| title | A carbohydrate-antioxidant hybrid polymer reduces oxidative damage in spermatozoa and enhances fertility |
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