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Development of monoclonal and recombinant antibodies and immunoassays for the most toxic coplanar polychlorinated biphenyls.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Development of monoclonal and recombinant antibodies and immunoassays for the most toxic coplanar polychlorinated biphenyls./
作者:	Chiu, Ya-Wen.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2002,
面頁冊數:	172 p.
附註:	Source: Dissertations Abstracts International, Volume: 64-06, Section: B.
Contained By:	Dissertations Abstracts International64-06B.
標題:	Environmental science. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3063627
ISBN:	9780493825687

Development of monoclonal and recombinant antibodies and immunoassays for the most toxic coplanar polychlorinated biphenyls.
Chiu, Ya-Wen.

Development of monoclonal and recombinant antibodies and immunoassays for the most toxic coplanar polychlorinated biphenyls. - Ann Arbor : ProQuest Dissertations & Theses, 2002 - 172 p.

Source: Dissertations Abstracts International, Volume: 64-06, Section: B.

Thesis (Ph.D.)--University of California, Berkeley, 2002.

This item must not be sold to any third party vendors.

Polychlorinated biphenyls (PCBs) are global pollutants with diverse toxic, reproductive, developmental, immunotoxic, and tumorigenic effects. Reliable congener-specific analysis would enhance toxicological studies, risk assessment and remediation. Three of the most toxic, least abundant and difficult to quantify of the 209 PCB congeners, 3,4,3',4' -tetrachlorobiphenyl, 3,4,3',4' ,5'-pentachlorobiphenyl, and 3,4,5,3' ,4',5'-hexachlorobiphenyl (PCBs 77, 126, and 169, respectively), can assume a coplanar conformation. A monoclonal antibody (MAb) designated S2B1 was derived, using a novel immunizing hapten that mimicked the chlorination pattern characteristic of coplanar congeners. Direct and indirect competitive enzyme immunoassays (EIAs) using MAb S2B1 and more weakly bound competitor haptens were highly specific for coplanar congeners, and did not recognize the more prevalent but much less toxic non-coplanar PCB congeners, 2,3,7,8-tetrachlorodibenzo-p-dioxin, 2,3,7,8-tetrachlorodibenzofuran, or dichlorobenzenes. To date, this is the first and only antibody and immunoassay specific for individual PCB congeners. The binding rates and affinity of MAb S2B1 for representative PCB congeners were determined by kinetic exclusion immunoassay (KinExA). This method showed that mono- and di-ortho chlorinated PCBs were recognized by MAb S2B1, but the on-rates were slower, and the off-rates were faster by 10 to 100-fold, compared to those with the coplanar congeners. This binding interaction which is not detectable by EIA, has important implications for engineering of PCB antibodies. Recombinant Fab antibodies (rFabs) were derived from hybridoma S2B1, and expressed as soluble rFabs in E. coli. Two rFab clones bound PCBs 77 and 126 with half-maximal inhibition of 10-13 ppb in EIAs, with selectivity nearly identical to that of whole S2B1 IgG and its proteolytic Fab fragments. These results, and comparison of amino acid sequences of MAb S2B1 and the rFab, proved that rFab S2B1 was a faithful copy of the MAb. The rFab S2B1 sequences had >75% identity with antibodies that bind nitrophenyl haptens. The results of this project make it possible to construct a 3-dimensional computational model of the PCB binding site, deduce binding interactions of PCBs with antibodies and naturally occurring PCB-binding proteins, and determine whether binding requires a conformational change in the PCB and/or the protein.

ISBN: 9780493825687Subjects--Topical Terms:

677245
Environmental science.
Subjects--Index Terms:

Immunoassays

Development of monoclonal and recombinant antibodies and immunoassays for the most toxic coplanar polychlorinated biphenyls.
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506 $a This item must not be sold to any third party vendors.
506 $a This item must not be added to any third party search indexes.
520 $a Polychlorinated biphenyls (PCBs) are global pollutants with diverse toxic, reproductive, developmental, immunotoxic, and tumorigenic effects. Reliable congener-specific analysis would enhance toxicological studies, risk assessment and remediation. Three of the most toxic, least abundant and difficult to quantify of the 209 PCB congeners, 3,4,3',4' -tetrachlorobiphenyl, 3,4,3',4' ,5'-pentachlorobiphenyl, and 3,4,5,3' ,4',5'-hexachlorobiphenyl (PCBs 77, 126, and 169, respectively), can assume a coplanar conformation. A monoclonal antibody (MAb) designated S2B1 was derived, using a novel immunizing hapten that mimicked the chlorination pattern characteristic of coplanar congeners. Direct and indirect competitive enzyme immunoassays (EIAs) using MAb S2B1 and more weakly bound competitor haptens were highly specific for coplanar congeners, and did not recognize the more prevalent but much less toxic non-coplanar PCB congeners, 2,3,7,8-tetrachlorodibenzo-p-dioxin, 2,3,7,8-tetrachlorodibenzofuran, or dichlorobenzenes. To date, this is the first and only antibody and immunoassay specific for individual PCB congeners. The binding rates and affinity of MAb S2B1 for representative PCB congeners were determined by kinetic exclusion immunoassay (KinExA). This method showed that mono- and di-ortho chlorinated PCBs were recognized by MAb S2B1, but the on-rates were slower, and the off-rates were faster by 10 to 100-fold, compared to those with the coplanar congeners. This binding interaction which is not detectable by EIA, has important implications for engineering of PCB antibodies. Recombinant Fab antibodies (rFabs) were derived from hybridoma S2B1, and expressed as soluble rFabs in E. coli. Two rFab clones bound PCBs 77 and 126 with half-maximal inhibition of 10-13 ppb in EIAs, with selectivity nearly identical to that of whole S2B1 IgG and its proteolytic Fab fragments. These results, and comparison of amino acid sequences of MAb S2B1 and the rFab, proved that rFab S2B1 was a faithful copy of the MAb. The rFab S2B1 sequences had >75% identity with antibodies that bind nitrophenyl haptens. The results of this project make it possible to construct a 3-dimensional computational model of the PCB binding site, deduce binding interactions of PCBs with antibodies and naturally occurring PCB-binding proteins, and determine whether binding requires a conformational change in the PCB and/or the protein.
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