Synthesis of Nicotinic Receptor Ligands and Strigolactones

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Material Information

Title:
Synthesis of Nicotinic Receptor Ligands and Strigolactones
Physical Description:
1 online resource (362 p.)
Language:
english
Creator:
Chojnacka, Kinga
Publisher:
University of Florida
Place of Publication:
Gainesville, Fla.
Publication Date:

Thesis/Dissertation Information

Degree:
Doctorate ( Ph.D.)
Degree Grantor:
University of Florida
Degree Disciplines:
Chemistry
Committee Chair:
HORENSTEIN,NICOLE ALANA
Committee Co-Chair:
STEWART,JON DALE
Committee Members:
BRUNER,STEVEN DOUGLAS
APONICK,AARON
PAPKE,ROGER LEE

Subjects

Subjects / Keywords:
7 -- acetylcholine -- agonist -- alpha -- desensitization -- nicotinic -- receptor -- silent -- strigolactones
Chemistry -- Dissertations, Academic -- UF
Genre:
Chemistry thesis, Ph.D.
bibliography   ( marcgt )
theses   ( marcgt )
government publication (state, provincial, terriorial, dependent)   ( marcgt )
born-digital   ( sobekcm )
Electronic Thesis or Dissertation

Notes

Abstract:
The first part of this dissertation is focused on the design and synthesis of molecules that differentially regulate activation and desensitization of the human alpha7 nicotinic acetylcholine receptor (nAChR). Alpha7 nAChR is a pentameric ligand gated ion channel that is currently a drug target for Alzheimer’s disease, schizophrenia and inflammatory disorders. Emerging evidence suggests that alpha7 in non-neuronal cells may inhibit pro-inflammatory cytokine production by a signaling mechanism that does not involve ion channel opening.  The term “silent agonists” is introduced to describe receptor ligands that bind to the conventional acetylcholine binding site, do not initiate ion channel activity, and place the receptor in a desensitized state that can be revealed in the presence of a type II positive allosteric modulator. Because these molecules convert the alpha7 nAChR from a resting state selectively into a desensitized state that can be probed by a type II PAM, they are of interest as a tool to study the functions of the alpha7 nAChR that do not involve ion conducting states, and may constitute a new modality for the development of alpha7 nAChR therapeutics. Three groups of silent agonists are characterized: the first group is represented by newly designed and synthesized KC-1 and KC-5 compounds, the second group features bulky quaternary ammonium compounds of appropriate molecular volume, and the third is exemplified by pyridinylmethylene anabaseines (PABs). The second part of this dissertation is focused on the strigolactone synthesis and biosynthesis. Strigolactones are a new class of plant hormones that inhibit shoot lateral branching. Synthesis of the strigolactone ABC-core in one step from linear precursors by an acid-catalyzed double cyclization was proposed and tested. Linear model precursors were prepared and conditions under which these molecules undergo the proposed double cyclization in good yields and with a high degree of stereocontrol were identified. These cyclization results are relevant because they suggest a plausible mechanism along the strigolactone biosynthetic pathway.
General Note:
In the series University of Florida Digital Collections.
General Note:
Includes vita.
Bibliography:
Includes bibliographical references.
Source of Description:
Description based on online resource; title from PDF title page.
Source of Description:
This bibliographic record is available under the Creative Commons CC0 public domain dedication. The University of Florida Libraries, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.
Statement of Responsibility:
by Kinga Chojnacka.
Thesis:
Thesis (Ph.D.)--University of Florida, 2013.
Local:
Adviser: HORENSTEIN,NICOLE ALANA.
Local:
Co-adviser: STEWART,JON DALE.
Electronic Access:
RESTRICTED TO UF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE UNTIL 2015-12-31

Record Information

Source Institution:
UFRGP
Rights Management:
Applicable rights reserved.
Classification:
lcc - LD1780 2013
System ID:
UFE0046141:00001