The overall objectives of this research are to gain a deeper understanding of the mechanism by which molecular umbrellas transport polar molecules across lipid bilayers, to define the scope of molecular umbrella-assisted bilayer transport, and to develop cleavable molecular umbrella conjugates with a view towards the development of prodrugs. The long-term goal of this program is to develop molecular umbrellas as membrane transporters of biologically-active agents for oral delivery, for delivery across the blood-brain barrier, and for gene therapy.
The specific aims for the current funding period include: (1) clarifying the interactions between molecular umbrella- glutathione conjugates and phospholipid membranes, (2) characterizing the transport properties of molecular umbrella- glutathione conjugates, (3) defining the influence of cholesterol on the bilayer transport properties of a molecular umbrella- peptide conjugate, (4) defining the influence of facial hydrophilicity on membrane transport, (5) testing for """"""""needle and thread"""""""" properties of molecular umbrella-oligoserine conjugates, (6) testing for """"""""needle and thread"""""""" properties of a molecular umbrella-oligonucleotide conjugate, and (7) synthesizing molecular umbrella conjugates that can release biologically- active peptides in their free form.
| Janout, Vaclav; Cline, Lauren L; Feuston, Bradley P et al. (2014) Molecular umbrella conjugate for the ocular delivery of siRNA. Bioconjug Chem 25:197-201 |
| Cline, Lauren L; Janout, Vaclav; Fisher, Michael et al. (2011) A molecular umbrella approach to the intracellular delivery of small interfering RNA. Bioconjug Chem 22:2210-6 |
| Janout, Vaclav; Regen, Steven L (2009) Bioconjugate-based molecular umbrellas. Bioconjug Chem 20:183-92 |
| Petrov, Ravil R; Chen, Wen-Hua; Regen, Steven L (2009) Thermally gated liposomes: a closer look. Bioconjug Chem 20:1037-43 |
| Mehiri, Mohamed; Chen, Wen-Hua; Janout, Vaclav et al. (2009) Molecular umbrella transport: exceptions to the classic size/lipophilicity rule. J Am Chem Soc 131:1338-9 |
| Chen, Wen-Hua; Janout, Vaclav; Kondo, Masaharu et al. (2009) A fine line between molecular umbrella transport and ionophoric activity. Bioconjug Chem 20:1711-5 |
| Kondo, Masaharu; Mehiri, Mohamed; Regen, Steven L (2008) Viewing membrane-bound molecular umbrellas by parallax analyses. J Am Chem Soc 130:13771-7 |
| Mehiri, Mohamed; Jing, Bingwen; Ringhoff, Danielle et al. (2008) Cellular entry and nuclear targeting by a highly anionic molecular umbrella. Bioconjug Chem 19:1510-3 |
| Liu, Guozheng; Hnatowich, Donald J (2008) A semiempirical model of tumor pretargeting. Bioconjug Chem 19:2095-104 |
| Madan, Rebecca Pellett; Mesquita, Pedro M M; Cheshenko, Natalia et al. (2007) Molecular umbrellas: a novel class of candidate topical microbicides to prevent human immunodeficiency virus and herpes simplex virus infections. J Virol 81:7636-46 |
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