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First Supramolecular Fluorescence-Based Assay for Carbonic Anhydrase Inhibitors

Koutnik, Petr
http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1471261858

Abstract Details

2016, Doctor of Philosophy (Ph.D.), Bowling Green State University, Photochemical Sciences.
This work presents supramolecular fluorescent probes capable of specific detection of carbonic anhydrases (CAs), a biologically and clinically important family of metalloenzymes implicated in certain pathological health conditions in humans. The probes, comprising 1,3,4-thiadiazol-5-yl-2-sulfonamide high-affinity moiety, were employed in fluorescence titrations with CAs and showed highly variable analyte-dependent change in fluorescence intensity. Moreover, the probes were utilized in competitive fluorescence-based assay to investigate affinity of model carbonic anhydrase inhibitors towards CAs. The probes were utilized in a competitive sensor array using simple instrumentation under high throughput screening settings. The excellent capability of recognizing a large number of structurally distinct CAIs at various concentrations was demonstrated in qualitative as well as quantitative assays. The throughput, sensitivity and limit of detection surpass the current state-of-the-art methods that generally require enzyme-linked immunosorbent assay based protocols and/or computational modeling. This study opens a new avenue for the development of simple high-throughput assays for the drug development and drugs candidates structure optimization in the near future. To the best of our knowledge, this study presents the first supramolecular fluorescence-based assay for carbonic anhydrase inhibitors.
Pavel Anzenbacher, Jr. (Advisor)
Haowen Xi (Other)
Marshall Wilson (Committee Member)
Jeremy Klosterman (Committee Member)
347 p.
Chemistry
fluorescent sensors; carbonic anhydrase; molecular docking; supramolecular sensing; anions; nerve gas agents; phosphonate; fluorescence

Recommended Citations

Citations

  • Koutnik, P. (2016). First Supramolecular Fluorescence-Based Assay for Carbonic Anhydrase Inhibitors [Doctoral dissertation, Bowling Green State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1471261858

    APA Style (7th edition)

  • Koutnik, Petr. First Supramolecular Fluorescence-Based Assay for Carbonic Anhydrase Inhibitors. 2016. Bowling Green State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1471261858.

    MLA Style (8th edition)

  • Koutnik, Petr. "First Supramolecular Fluorescence-Based Assay for Carbonic Anhydrase Inhibitors." Doctoral dissertation, Bowling Green State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1471261858

    Chicago Manual of Style (17th edition)

bgsu1471261858
488
© 2016, all rights reserved.
This open access ETD is published by Bowling Green State University and OhioLINK.