The Development of Potential Therapeutic Anti-Myosin S2 Peptides that Modulate Contraction and Append to the Heart Homing Adduct Tannic Acid without Noticeable Effect on Their Functions

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This dissertation aimed to explore the S2 region with an attempt to modulate its elasticity in order to tune the contraction output. Two peptides, the stabilizer and destabilizer, showed high potential in modifying the S2 region at the cellular level, thus they were prepared for animal model testing. In this research, (i) S2 elasticity was studied, and the stabilizer and destabilizer peptides were built to tune contraction output through modulating S2 flexibility; (ii) the peptides were attached to heart homing adducts and the bond between them was confirmed; and (iii) it was shown that minor changes were imposed on the … continued below

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xiii, 76 pages

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Qadan, Motamed May 2021.

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This dissertation aimed to explore the S2 region with an attempt to modulate its elasticity in order to tune the contraction output. Two peptides, the stabilizer and destabilizer, showed high potential in modifying the S2 region at the cellular level, thus they were prepared for animal model testing. In this research, (i) S2 elasticity was studied, and the stabilizer and destabilizer peptides were built to tune contraction output through modulating S2 flexibility; (ii) the peptides were attached to heart homing adducts and the bond between them was confirmed; and (iii) it was shown that minor changes were imposed on the modulating peptides' functionality upon attaching to the heart homing adducts. S2 flexibility was confirmed through comparing it to other parts of myosin using simulated force spectroscopy. Modulatory peptides were built and computationally tested for their efficacy through interaction energy measurement, simulated force spectroscopy and molecular dynamics; these were attached to heart homing adducts for heart delivery. Interaction energy tests determined that tannic acid (TA) served well for this purpose. The stoichiometry of the bond between the TA and the modulating peptides was confirmed using mass spectroscopy. The functionality of the modulating peptides was shown to be unaltered through expansion microscopy where they located to the same position on the sarcomere with and without TA. They were also shown to cause the sarcomeres to contract similarly with and without the TA in contractility assay. Taken together, this work prepared the modulating peptides for animal model tests by attaching them to tannic acid.

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xiii, 76 pages

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  • May 2021

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  • May 26, 2021, 9:38 p.m.

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  • March 22, 2022, 3:26 p.m.

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Qadan, Motamed. The Development of Potential Therapeutic Anti-Myosin S2 Peptides that Modulate Contraction and Append to the Heart Homing Adduct Tannic Acid without Noticeable Effect on Their Functions, dissertation, May 2021; Denton, Texas. (https://digital.library.unt.edu/ark:/67531/metadc1808423/: accessed May 26, 2024), University of North Texas Libraries, UNT Digital Library, https://digital.library.unt.edu; .

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