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Promotion and Inhibition of Molecular Recognition at Interfaces in Aqueous Solution

Ma, Mingming
http://rave.ohiolink.edu/etdc/view?acc_num=osu1291136621

Abstract Details

2010, Doctor of Philosophy, Ohio State University, Chemistry.
This dissertation is composed of all of my efforts devoted into two research projects. The first project (chapter 2-5) includes five designed molecular recognition systems in aqueous solutions. The second project (chapter 6) focuses on using sugar-lipid conjugates to protect liposomes from serum protein binding, and to protect supported lipid bilayer from damage during dehydration and rehydration. At the beginning of the first project, we designed, synthesized and studied a novel monovalent hydrogen bonding phospholipid system, using cyanuric acid (CA) and melamine (M) as the recognition pair. Our study has confirmed that the selective heteromeric membrane apposition was due to the molecular recognition between CA and M groups on the membrane surface. However, the major limitation of this monovalent system is that: the requisite density of CA/M modules for recognition was quite high. Trying to find the minimal valency required for the detectable lipid-lipid binding, we designed, synthesized and studied our second CA/M phospholipid system: the trivalent system. Our studies have revealed that low membrane concentrations of the trivalent CA/M lipids or peptides retained the robust molecular recognition properties found with surfaces composed entirely of monovalent CA/M lipids, although membrane activation upon binding was diminished. The robust molecular recognition of CA/M at the lipid-water interface promotes our efforts to extend the application to other apolar-water interfaces. As the first step, we still focused on the lipid-water interface. Instead of using functionalized lipids, we switched to amphiphilic peptides, specifically magainin. By covalently attaching the CA/M recognition motifs to magainin peptides, we found that these new peptide conjugates bound lipid membrane in a cooperative manner, and also their membrane activity was greatly enhanced. As the second step, we extended our interest further to protein-protein interfaces. We chose streptavidin, a well studied and widely used tetrameric protein. Synthesized biotin derivatives bearing the CA/M recognition motifs, and incorporated them onto streptavidin through biotin-streptavidin binding, we found that these functionalized streptavidin proteins could bind each other in a temperature-dependent and reversible manner. Curious about the mechanism and driving force of the CA-M interaction at various interfaces, we investigated the small molecule CA-M self-assembly in an aqueous solution at no interface. The parent CA-M self-assembly appears to be driven in large part by hydrophobic burial or “base-stacking” effects in water. The examination of aqueous-phase recognition between the trivalent derivatives, TCA and TM, suggests the possibility of designing useful recognition modules that function in water, as trivalent presentation of the heterocycles on a solubilizing molecular scaffold was found to enhance recognition and limit aggregate precipitation. For the second project, we switched our focus to preventing non-specific molecular interaction at the lipid-water interface, especially between serum proteins and liposomes. The non-specific serum protein-lipid binding is the main barrier for creating long-circulating lipid vesicle carrier. We designed and synthesized novel glycolipid polymers that provide vesicle stability in serum as well as unprecedented anhydrobiotic and cryoprotective properties. We anticipate that this glycolipid system will be useful for the stabilization of synthetic membranes for delivery and SLB bioanalytical devices.
Dennis Bong, PhD (Advisor)
Dehua Pei, PhD (Committee Member)
Jonathon Parquette, PhD (Committee Member)
Carole Fink, PhD (Committee Member)
256 p.
Biomedical Research; Biophysics; Materials Science; Molecular Chemistry; Organic Chemistry
molecular recognition; interface; hydrogen bonding; cyanuric acid; melamine; base stacking; hydrophobic effect; supported lipid bilayer; drug delivery carrier; trehalose

Recommended Citations

Citations

  • Ma, M. (2010). Promotion and Inhibition of Molecular Recognition at Interfaces in Aqueous Solution [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1291136621

    APA Style (7th edition)

  • Ma, Mingming. Promotion and Inhibition of Molecular Recognition at Interfaces in Aqueous Solution. 2010. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1291136621.

    MLA Style (8th edition)

  • Ma, Mingming. "Promotion and Inhibition of Molecular Recognition at Interfaces in Aqueous Solution." Doctoral dissertation, Ohio State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=osu1291136621

    Chicago Manual of Style (17th edition)

osu1291136621
348
© 2010, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.