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Synthesis and Study of Membrane Active Compounds

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posted on 2008-07-18, 00:00 authored by Edward J O'Neil
This dissertation describes the design, synthesis, and activity of molecules that interact specifically with vesicle or cellular membranes. The first section describes a series of second generation Zn2+ bis DPA coordination complexes that selectively target negatively charged membrane surfaces including those found in apoptotic cells and bacteria. Several types of conjugates were constructed including fluorescent versions suitable for microscopy, multivalent receptors designed for increased membrane affinity, and lipophilic derivatives. The synthesis and membrane activity of each is discussed. The second portion of this dissertation describes general strategies for the synthesis of sn-2 functionalized phospholipids from DPPC. Phospholipases were utilized for selective headgroup and side chain modification of commercially available phospholipids circumventing a de novo synthetic approach. Several classes of functionalized phosphatidylcholine derivatives were constructed including bolaamphiphiles which in some cases were found to destabilize membranes and chloride anion transporters that function by a novel relay mechanism. Other phospholipid derivatives include phosphatidylserine and phosphatidylethanolamine conjugates that were designed for receptor-mediated delivery of cargo into cells.

History

Date Modified

2017-06-02

Defense Date

2008-06-27

Research Director(s)

Professor Shahriar Mobashery

Committee Members

Professor Paul Helquist Professor Shahriar Mobashery Professor Richard E. Taylor

Degree

  • Doctor of Philosophy

Degree Level

  • Doctoral Dissertation

Language

  • English

Alternate Identifier

etd-07182008-103101

Publisher

University of Notre Dame

Program Name

  • Chemistry and Biochemistry

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