Electrochemical Immunosensors for Effective Evaluation of Amyloid-Beta Modulators on Oligomeric and Fibrillar Aggregation Processes
A novel electrochemical immunosensor fabricated from gold compact disc electrodes was designed for rapid evaluation of aggregation processes that lead to the formation of oligomeric and fibrillar states of amyloid-beta1–42 (Aβ1–42) during Alzheimer’s disease. Conformation-specific antibodies were im...
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| Veröffentlicht in: | Analytical chemistry (Washington) 2014-05, Vol.86 (10), p.4901-4909 |
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| creator | Veloso, Anthony J Chow, Ari M Ganesh, Hashwin V. S Li, Nan Dhar, Devjani Wu, David C. H Mikhaylichenko, S Brown, Ian R Kerman, Kagan |
| description | A novel electrochemical immunosensor fabricated from gold compact disc electrodes was designed for rapid evaluation of aggregation processes that lead to the formation of oligomeric and fibrillar states of amyloid-beta1–42 (Aβ1–42) during Alzheimer’s disease. Conformation-specific antibodies were immobilized on the surface of the gold electrode using a 3,3′-dithiobis (sulfosuccinimidyl) propionate (DTSSP) linker. Surface binding events were analyzed by electrochemical impedance spectroscopy (EIS) in which the formation of an antigen–antibody complex was quantified as a function of charge transfer resistance using a [Fe(CN)6]3–/4– redox probe. The effectiveness of novel sym-triazine-derived aggregation modulators (TAE-1, TAE-2) to reduce the population of toxic oligomers was evaluated. Aβ fibril formation was validated by thioflavin T (ThT) fluorescence, whereas oligomer formation was investigated by MALDI. Antigen detection by EIS was further supported by immuno dot blot assays for oligomeric and fibrillar components. Docking simulations of the aggregation modulators TAE-1 and TAE-2 with Aβ1–42 fibrils performed using Autodock Vina suggest a mechanism for the improved aggregation inhibition observed for TAE-2. The results demonstrate the utility and convenience of impedance immunosensing as an analytical tool for rapid and comprehensive evaluation of effective Aβ aggregation modulating agents. |
| doi_str_mv | 10.1021/ac500424t |
| format | Article |
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S ; Li, Nan ; Dhar, Devjani ; Wu, David C. H ; Mikhaylichenko, S ; Brown, Ian R ; Kerman, Kagan</creator><creatorcontrib>Veloso, Anthony J ; Chow, Ari M ; Ganesh, Hashwin V. S ; Li, Nan ; Dhar, Devjani ; Wu, David C. H ; Mikhaylichenko, S ; Brown, Ian R ; Kerman, Kagan</creatorcontrib><description>A novel electrochemical immunosensor fabricated from gold compact disc electrodes was designed for rapid evaluation of aggregation processes that lead to the formation of oligomeric and fibrillar states of amyloid-beta1–42 (Aβ1–42) during Alzheimer’s disease. Conformation-specific antibodies were immobilized on the surface of the gold electrode using a 3,3′-dithiobis (sulfosuccinimidyl) propionate (DTSSP) linker. Surface binding events were analyzed by electrochemical impedance spectroscopy (EIS) in which the formation of an antigen–antibody complex was quantified as a function of charge transfer resistance using a [Fe(CN)6]3–/4– redox probe. The effectiveness of novel sym-triazine-derived aggregation modulators (TAE-1, TAE-2) to reduce the population of toxic oligomers was evaluated. Aβ fibril formation was validated by thioflavin T (ThT) fluorescence, whereas oligomer formation was investigated by MALDI. Antigen detection by EIS was further supported by immuno dot blot assays for oligomeric and fibrillar components. Docking simulations of the aggregation modulators TAE-1 and TAE-2 with Aβ1–42 fibrils performed using Autodock Vina suggest a mechanism for the improved aggregation inhibition observed for TAE-2. The results demonstrate the utility and convenience of impedance immunosensing as an analytical tool for rapid and comprehensive evaluation of effective Aβ aggregation modulating agents.</description><identifier>ISSN: 0003-2700</identifier><identifier>EISSN: 1520-6882</identifier><identifier>DOI: 10.1021/ac500424t</identifier><identifier>PMID: 24784791</identifier><identifier>CODEN: ANCHAM</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Agglomeration ; Alzheimer's disease ; Amyloid beta-Peptides - chemistry ; Amyloid beta-Peptides - drug effects ; Analytical chemistry ; Antigens ; Biosensing Techniques ; Electrochemical impedance spectroscopy ; Electrochemical Techniques - instrumentation ; Electrochemical Techniques - methods ; Electrodes ; Fluorescence ; Formations ; Gold ; Humans ; Immunochemistry - instrumentation ; Immunochemistry - methods ; Immunosensors ; Microelectrodes ; Modulators ; Oligomers ; Sensors ; Simulation</subject><ispartof>Analytical chemistry (Washington), 2014-05, Vol.86 (10), p.4901-4909</ispartof><rights>Copyright American Chemical Society May 20, 2014</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a376t-fbe01f918ebb8c0650ddf72b3db5c742d9e4c0a95a2f0751306f81bfc81801463</citedby><cites>FETCH-LOGICAL-a376t-fbe01f918ebb8c0650ddf72b3db5c742d9e4c0a95a2f0751306f81bfc81801463</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/ac500424t$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/ac500424t$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24784791$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Veloso, Anthony J</creatorcontrib><creatorcontrib>Chow, Ari M</creatorcontrib><creatorcontrib>Ganesh, Hashwin V. S</creatorcontrib><creatorcontrib>Li, Nan</creatorcontrib><creatorcontrib>Dhar, Devjani</creatorcontrib><creatorcontrib>Wu, David C. H</creatorcontrib><creatorcontrib>Mikhaylichenko, S</creatorcontrib><creatorcontrib>Brown, Ian R</creatorcontrib><creatorcontrib>Kerman, Kagan</creatorcontrib><title>Electrochemical Immunosensors for Effective Evaluation of Amyloid-Beta Modulators on Oligomeric and Fibrillar Aggregation Processes</title><title>Analytical chemistry (Washington)</title><addtitle>Anal. Chem</addtitle><description>A novel electrochemical immunosensor fabricated from gold compact disc electrodes was designed for rapid evaluation of aggregation processes that lead to the formation of oligomeric and fibrillar states of amyloid-beta1–42 (Aβ1–42) during Alzheimer’s disease. Conformation-specific antibodies were immobilized on the surface of the gold electrode using a 3,3′-dithiobis (sulfosuccinimidyl) propionate (DTSSP) linker. Surface binding events were analyzed by electrochemical impedance spectroscopy (EIS) in which the formation of an antigen–antibody complex was quantified as a function of charge transfer resistance using a [Fe(CN)6]3–/4– redox probe. The effectiveness of novel sym-triazine-derived aggregation modulators (TAE-1, TAE-2) to reduce the population of toxic oligomers was evaluated. Aβ fibril formation was validated by thioflavin T (ThT) fluorescence, whereas oligomer formation was investigated by MALDI. Antigen detection by EIS was further supported by immuno dot blot assays for oligomeric and fibrillar components. Docking simulations of the aggregation modulators TAE-1 and TAE-2 with Aβ1–42 fibrils performed using Autodock Vina suggest a mechanism for the improved aggregation inhibition observed for TAE-2. The results demonstrate the utility and convenience of impedance immunosensing as an analytical tool for rapid and comprehensive evaluation of effective Aβ aggregation modulating agents.</description><subject>Agglomeration</subject><subject>Alzheimer's disease</subject><subject>Amyloid beta-Peptides - chemistry</subject><subject>Amyloid beta-Peptides - drug effects</subject><subject>Analytical chemistry</subject><subject>Antigens</subject><subject>Biosensing Techniques</subject><subject>Electrochemical impedance spectroscopy</subject><subject>Electrochemical Techniques - instrumentation</subject><subject>Electrochemical Techniques - methods</subject><subject>Electrodes</subject><subject>Fluorescence</subject><subject>Formations</subject><subject>Gold</subject><subject>Humans</subject><subject>Immunochemistry - instrumentation</subject><subject>Immunochemistry - methods</subject><subject>Immunosensors</subject><subject>Microelectrodes</subject><subject>Modulators</subject><subject>Oligomers</subject><subject>Sensors</subject><subject>Simulation</subject><issn>0003-2700</issn><issn>1520-6882</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpl0U1P3DAQBmCrKioL9NA_UFmqkOghdMb5co7LammRFtEDPUeOM16MnJjaCRJn_jhGSxEqJx_8-J2RX8a-IJwiCPyhdAlQiGL6wBZYCsgqKcVHtgCAPBM1wD47iPEWABGw-sT2RVHLom5wwR7XjvQUvL6hwWrl-MUwzKOPNEYfIjc-8LUxidh74ut75WY1WT9yb_hyeHDe9tkZTYpf-n52anp-k26vnN36gYLVXI09P7ddsM6pwJfbbaDtLuJ3mkoxUjxie0a5SJ9fzkP253x9vfqVba5-XqyWm0zldTVlpiNA06CkrpMaqhL63tSiy_uu1HUh-oYKDaoplTBQl5hDZSR2RkuUgEWVH7KTXe5d8H9nilM72KgpLTaSn2OLVSNyCWVdJPrtP3rr5zCm7Vos8_SNUghI6vtO6eBjDGTau2AHFR5ahPa5mfa1mWS_viTO3UD9q_xXRQLHO6B0fDPtXdATLtuWHQ</recordid><startdate>20140520</startdate><enddate>20140520</enddate><creator>Veloso, Anthony J</creator><creator>Chow, Ari M</creator><creator>Ganesh, Hashwin V. 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Conformation-specific antibodies were immobilized on the surface of the gold electrode using a 3,3′-dithiobis (sulfosuccinimidyl) propionate (DTSSP) linker. Surface binding events were analyzed by electrochemical impedance spectroscopy (EIS) in which the formation of an antigen–antibody complex was quantified as a function of charge transfer resistance using a [Fe(CN)6]3–/4– redox probe. The effectiveness of novel sym-triazine-derived aggregation modulators (TAE-1, TAE-2) to reduce the population of toxic oligomers was evaluated. Aβ fibril formation was validated by thioflavin T (ThT) fluorescence, whereas oligomer formation was investigated by MALDI. Antigen detection by EIS was further supported by immuno dot blot assays for oligomeric and fibrillar components. Docking simulations of the aggregation modulators TAE-1 and TAE-2 with Aβ1–42 fibrils performed using Autodock Vina suggest a mechanism for the improved aggregation inhibition observed for TAE-2. The results demonstrate the utility and convenience of impedance immunosensing as an analytical tool for rapid and comprehensive evaluation of effective Aβ aggregation modulating agents.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>24784791</pmid><doi>10.1021/ac500424t</doi><tpages>9</tpages></addata></record> |
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| subjects | Agglomeration Alzheimer's disease Amyloid beta-Peptides - chemistry Amyloid beta-Peptides - drug effects Analytical chemistry Antigens Biosensing Techniques Electrochemical impedance spectroscopy Electrochemical Techniques - instrumentation Electrochemical Techniques - methods Electrodes Fluorescence Formations Gold Humans Immunochemistry - instrumentation Immunochemistry - methods Immunosensors Microelectrodes Modulators Oligomers Sensors Simulation |
| title | Electrochemical Immunosensors for Effective Evaluation of Amyloid-Beta Modulators on Oligomeric and Fibrillar Aggregation Processes |
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