PTEN-5-HT2CR Complex: An Ideal Target for Developing Treatment to Restore the Functioning of 5-HT2CR; An Attempt to Minimize the Development of Antimicrobial Resistance

dc.contributor.advisorGilbertson, Scott R.
dc.contributor.committeeMemberDaugulis, Olafs
dc.contributor.committeeMemberColtart, Don M.
dc.contributor.committeeMemberChen, Tai-Yen
dc.contributor.committeeMemberCuny, Gregory D.
dc.creatorJi, Haofan 1992- 2018 2018
dc.description.abstractPART I ABSTRACT Serotonin 2C receptor (5-HT2CR) plays an important role in the regulation of neurotransmission disorders and maybe an ideal target to develop treatments for drug addiction. The coupling between the 5-HT2CR and protein phosphatase and tensin homologue (PTEN) limited the activity of the receptor. The disruption of the interaction has been demonstrated to restore the activity of 5-HT2CR. A key fragment (3L4F-F1) of 5-HT2CR can disrupt the interaction between 5-HT2CR and PTEN. To mimic this fragment, an alanine scan was utilized. The results show that Asn(I), Asp, Asn(II), and Arg are the key amino acids for the bioactivity. A β-turn template was synthesized to develop physiologically-stable inhibitors. The β-turn peptidomimetic shows good biological activity and will be utilized to guide the development of future molecules. PART II ABSTRACT Antimicrobial resistance is a growing public health threat and observed in bacteria that cause common health problems and infections. Aminoacyl-tRNA synthetases (AsRSs) which use a unique two-step mechanism of aminoacylation reaction are ideal targets for antibacterials. AN2690, a benzoxaborole derivative, shows great antibiotic activity by trapping tRNALeu in the editing domain. Inspired by AN2690 and other benzoxaborole derivatives, we designed (S)-3-Aminomethyl-7-(3-hydroxy-propoxy)-3H-benzo[c][1,2]oxaborol-1-ol to block the editing domain. A rationally stable analogue of Leu-AMP intermediate was designed to block the active site. After linking them together, we hope this dimer can target the editing domain and the catalytic domain simultaneously to minimize the development of antimicrobial resistance.
dc.description.departmentChemistry, Department of
dc.format.digitalOriginborn digital
dc.rightsThe author of this work is the copyright owner. UH Libraries and the Texas Digital Library have their permission to store and provide access to this work. Further transmission, reproduction, or presentation of this work is prohibited except with permission of the author(s).
dc.subjectSerotonin receptor
dc.subjectDrug addiction
dc.subjectProtein phosphatase and tensin homologue
dc.subjectΒ-turn template
dc.subjectAntimicrobial resistance
dc.subjectAminoacyl-tRNA synthetases
dc.subjectBenzoxaborole derivative
dc.subjectEditing domain
dc.subjectActive sites
dc.titlePTEN-5-HT2CR Complex: An Ideal Target for Developing Treatment to Restore the Functioning of 5-HT2CR; An Attempt to Minimize the Development of Antimicrobial Resistance
local.embargo.terms2020-08-01 of Natural Sciences and Mathematics, Department of of Houston of Science


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