Synthetic mimics of mammalian cell surface receptors: method and compositions
AssigneeThe Penn State Research Foundation
InventorsBLAKE R. PETERSON, QI SUN
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Abstract
The present invention relates to new synthetic receptors. More particularly, the present invention relates to methods for synthesizing preferred membrane-binding elements, preferably cholesterylamine derivatives, including 3β-amino-5-cholestene (3β-cholesterylamine) and related 3β-halides through i-steroid and retro-i-steroid rearrangements. The invention further relates to use of the synthetic receptors for delivering a protein, peptide, drug, prodrug, lipid, nucleic acid, carbohydrate or small molecule into a target cell via receptor-mediated endocytosis. According to the invention, novel synthetic mimics of cell surface receptors have been designed and methods for use of the same are disclosed.
Claims13
A method for synthesis of 3β-amino-5-cholestene or a related 3β-halide comprising:
- reacting cholesterol or a cholesterol derivative with a Lewis acid and an azide to form 3β-azido-5-cholestene;
- and
- reducing 3β-azido-5-cholestene to obtain 3β-amino-5-cholestene;
- or reacting cholesterol or a cholesterol derivative with a Lewis acid to afford a related 3β-halide.
A method of synthesizing a β-stereochemistry cholestene-derived membrane-binding element comprising:
- undergoing i-steroid or retro-i-steroid rearrangement of cholesterol or a cholesterol derivative using a Lewis acid and azide to generate a 3β-azido-5-cholestene;
- and
- reducing said 3β-azido-5-cholestene to obtain a 3β-amino-5-cholestene or related membrane-binding element.
A synthetic cell receptor for delivering a target into a cell comprising:
- a target-binding motif;
- and
- a linker region linking a membrane-binding element with the target-binding motif, wherein linker region comprises at least one subunit of beta-alanine, and wherein the membrane-binding element is a derivative of 3β-cholesterylamine maintaining β-stereochemistry and has the formula of:
- wherein the R is an N-alkyl, N-aryl or N-acyl derivative of 3β-cholesterylamine and wherein said element anchors said receptor into a cell plasma membrane.
Dependencies are inferred from the claim text.