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Design, synthesis, and characterization of bioactive amphiphiles for therapeutic applications

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TitleInfo
Title
Design, synthesis, and characterization of bioactive amphiphiles for therapeutic applications
Name (type = personal)
NamePart (type = family)
Faig
NamePart (type = given)
Allison Marie
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Allison Marie Faig
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author
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Uhrich
NamePart (type = given)
Kathryn E.
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Kathryn E. Uhrich
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Advisory Committee
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chair
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Romsted
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Laurence
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Laurence Romsted
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Advisory Committee
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internal member
Name (type = personal)
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Warmuth
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Ralf
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Ralf Warmuth
Affiliation
Advisory Committee
Role
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internal member
Name (type = personal)
NamePart (type = family)
Mintzer
NamePart (type = given)
Evan
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Evan Mintzer
Affiliation
Advisory Committee
Role
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outside member
Name (type = corporate)
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Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
Graduate School - New Brunswick
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RoleTerm (authority = RULIB)
school
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Text
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theses
OriginInfo
DateCreated (encoding = w3cdtf); (qualifier = exact)
2015
DateOther (qualifier = exact); (type = degree)
2015-10
CopyrightDate (encoding = w3cdtf); (qualifier = exact)
2015
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
Amphiphilic molecules are comprised of hydrophobic and hydrophilic domains. These molecules possess diverse chemical structures, which govern their physicochemical and biological properties, and these properties dictate amphiphiles’ use in various applications. This dissertation focuses on the design, synthesis, and characterization of amphiphiles for biomedical applications. Amphiphilic macromolecules (AMs), comprised of an acylated sugar backbone conjugated to a hydrophilic poly(ethylene glycol), were investigated as atherosclerosis treatments. Atherosclerosis is characterized by the accumulation and macrophage-mediated uptake of oxidized low-density lipoprotein (oxLDL). Previous studies indicate that AMs competitively inhibit oxLDL uptake through interacting with macrophage scavenger receptors, which contain hydrophobic and/or basic residues near their binding domains. Using knowledge of scavenger receptor binding domains, two AM series – termed ether- and alkyl-AMs – were designed to elucidate whether hydrogen-bonding or hydrophobic-hydrophobic interactions more significantly influenced bioactivity, respectively. Upon successful synthesis of each series, AM physicochemical and biological properties were assessed. More hydrophobic AMs, possessing longer and/or alkyl-terminated (i.e., alkyl-AMs) acyl arms, exhibited enhanced oxLDL uptake inhibition and thus improved bioactivity. These studies demonstrated that hydrophobic interactions significantly influence anti-atherosclerotic activity. Biscationic tartaric acid-based amphiphiles were also investigated for antimicrobial applications. Cationic amphiphiles exhibit unique membrane-disrupting bactericidal mechanisms via a combination of electrostatic and hydrophobic-hydrophobic interactions. This work explored the specific impact of charge location on cationic amphiphiles’ antimicrobial and membrane activity. Two series of analogous cationic amphiphiles were synthesized, termed gemini-like and bola-like, which differed only in their charge location. After successful synthesis, antimicrobial activity was assessed and lead compounds identified. Bola-like amphiphiles exhibited preferential activity against gram-positive bacteria, while gemini-like amphiphiles were more active against gram-negative bacteria. Biophysical experiments indicated that the lead gemini-like amphiphile interacted with model membranes via electrostatic interactions, whereas the lead bola-like amphiphile relied on a combination of electrostatic and hydrophobic interactions. These studies demonstrate the significant influence of charge location on cationic amphiphile antimicrobial and membrane activity.
Subject (authority = RUETD)
Topic
Chemistry and Chemical Biology
Subject (authority = ETD-LCSH)
Topic
Bioactive compounds
Subject (authority = ETD-LCSH)
Topic
Macromolecules
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_6458
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (xxi, 149 p. : ill.)
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Allison Marie Faig
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Location
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NjNbRU
Identifier (type = doi)
doi:10.7282/T3PV6NC0
Genre (authority = ExL-Esploro)
ETD doctoral
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RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Faig
GivenName
Allison
MiddleName
Marie
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2015-04-24 17:23:49
AssociatedEntity
Name
Allison Faig
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
Copyright
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Copyright protected
Availability
Status
Open
Reason
Permission or license
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ETD
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windows xp
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