Telodendrimer nanodiscs without apolipoprotein
AssigneeThe Regents of the University of California
InventorsKit S. Lam, Juntao Luo, Joyce S. Lee
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Abstract
The present invention provides a nanodisc without a membrane scaffold protein. The nanodisc includes a telodendrimer and a lipid; the nanodisc does not include a membrane scaffold protein. The telodendrimer has the general formula PEG-L-D-(R)n, wherein D is a dendritic polymer; L is a bond or a linker linked to the focal point group of the dendritic polymer; each PEG is a poly(ethylene glycol) polymer; each R is and end group of the dendritic polymer, or and end group with a covalently bound hydrophobic group, hydrophilic group, amphiphilic compound, or drug; and subscript n is an integer from 2 to 20. Methods of making the nanodiscs are also provided.
Claims21
A nanodisc without a membrane scaffold protein, the nanodisc comprising:
- a telodendrimer of formula I:
- (PEG)m-(A)p-L-D-(R)n (I)
- wherein
- D is a dendritic polymer having a single focal point group, a plurality of branched monomer units and a plurality of end groups,
- L is a bond or a linker linked to the focal point group of the dendritic polymer,
- each PEG is a polyethyleneglycol (PEG) polymer, wherein each PEG polymer has a molecular weight of 1-100 kDa,
- each R is independently selected from the group consisting of the end group of the dendritic polymer, a hydrophobic group, a hydrophilic group, an amphiphilic compound and a drug, such that when R is not an end group each R is linked to one of the end groups,
- subscript n is an integer from 2 to 20, wherein subscript n is equal to the number of end groups on the dendritic polymer, and wherein at least half the number n of R groups are each independently selected from the group consisting of a hydrophobic group, a hydrophilic group, an amphiphilic compound and a drug,
- subscript m is from 0 to 20,
- subscript p is 0 or 1, and
- radical A is a monomer or oligomer linked to at least two PEG groups;
- and
- a lipid,
- wherein the nanodisc does not include a membrane scaffold protein.
A method of making a nanodisc without a membrane scaffold protein, the method comprising:
- forming a reaction mixture comprising a lipid and a telodendrimer, wherein the lipid:telodendrimer ratio is from about 50:1 to about 1:50 (w/w), thereby preparing
- the nanodisc without a membrane scaffold. protein,
- wherein the telodendrimer is of formula I:
- (PEG)m-(A)p-L-D-(R)n (I)
- wherein
- D is a dendritic polymer having a single focal point group, a plurality of branched monomer units and a plurality of end groups,
- L is a bond or a linker linked to the focal point of the dendritic polymer,
- each PEG is a polyethyleneglycol (PEG) polymer, wherein each PEG polymer has a molecular weight of 1-100 kDa,
- each R is independently selected from the group consisting of the end group of the dendritic polymer, a hydrophobic group, a hydrophilic group, an amphiphilic compound and a drug, such that when R is not an end group each R is linked to one of the end groups,
- subscript n is an integer from 2 to 20, wherein subscript n is equal to the number of end groups on the dendriticsolymer, and wherein at least half the number n of groups are each independently selected from the group consisting of a hydrophobic group, a hydrophilic group, an arnphiphi lie compound and a drug,
- subscript m is from 0 to 20,
- subscript p is 0 or 1, and
- radical A is a monomer or oligomer linked to at least two PEG groups.
A nanodisc without a membrane scaffold protein, the nanodisc consisting essentially of:
- a telodendrimer having the formula:
- PEG-L-D(R)n
- wherein
- D is a dendritic polymer having a single focal point group, a plurality of branched monomer units and a plurality of end groups,
- L is a bond or a linker linked to the focal point group of the dendritic polymer,
- each PEG is a polyethyleneglycol (PEG) polymer, wherein each PEG polymer has a molecular weight of 1-100 kDa,
- each R is independently selected from the group consisting of the end group of the dendritic polymer, a hydrophobic group, a hydrophilic group, an amphiphilic compound and a drug, such that when R is not an end group each R is linked to one of the end groups, and
- subscript n is an integer from 2 to 20, wherein subscript n is equal to the number of end groups on the dendritic polymer, and wherein at least half the number n of R groups are each an amphiphilic compound;
- a lipid;
- and
- a drug,
- wherein the ratio of lipid to telodendrimer is from about 50:1 to about 1:50 (w/w).
Dependencies are inferred from the claim text.