'Molecular Umbrellas as Membrane Transporters'

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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.