Highly packed polycationic ammonium, sulfonium and phosphonium lipids
AssigneeLife Technologies Corporation
InventorsAlberto Haces, Valentina C. Ciccarone
Life of this patent
Estimating the term…
Abstract
The present invention discloses highly packed polycationic ammonium, sulfonium and phosphonium lipid compounds useful for making lipid aggregates for delivery of macromolecules and other compounds into cells. They are especially useful for the DNA-dependent transformation of cells. Methods for their preparation and use as intracellular delivery agents are also disclosed.
Claims61
A compound having the formula ##STR9## where x is an integer ranging from 1 to about 20;
- Y is an anion;
- and c is the number of positive charges in the compound divided by the valence of the anion;
- l, m and n are integers from 1 to about 6, except that at least one of l, m or n is 3 or less;
- R.sub.A and R.sub.B are selected from the group consisting of H or an alkyl, hydroxyalkyl, or thiol-substituted alkyl group having from 1 to about 6 carbon atoms;
- R.sub.1 -R.sub.4, independently of one another, are alkyl groups having 1 to 6 carbon atoms;
- A.sub.1 -A.sub.4, independently of one another, are straight-chain or branched alkyl, alkenyl or alkynyl groups having from 6 to about 22 carbon atoms, except that when x is 1 or 2, and when l, m, or n is an integer from 3 to 6, then A.sub.1, A.sub.2, A.sub.3, and A.sub.4 cannot be an alkyl group having less than 14 carbon atoms.
A polycation having the formula:
- ##STR10## where x is an integer ranging from 1 to about 20;
- l, m and n are integers from 1 to about 6, except that at least one of l, m or n is 3 or less;
- R.sub.A and R.sub.B are selected from the group consisting of H or an alkyl, hydroxyalkyl, or thiol-substituted alkyl group having from 1 to about 6 carbon atoms;
- R.sub.1 -R.sub.4, independently of one another, are alkyl groups having 1 to 6 carbon atoms;
- A.sub.1 -A.sub.4, independently of one another, are straight-chain or branched alkyl, alkenyl or alkynyl groups having from 6 to about 22 carbon atoms, except that when x is 1 or 2, when l, m, or n is an integer from 3 to 6, then A.sub.1, A.sub.2, A.sub.3, and A.sub.4 cannot be an alkyl group having less than 14 carbon atoms.
A lipid aggregate which comprises a compound having the formula ##STR11## wherein x is an from 1 to about 20;
- Y is an anion;
- c is the number of positive charges in the compound divided by the valency of the anion;
- n.sub.i, where i=1 to x, independently of one another, are integers varying from 1 to about 6;
- R.sub.A and R.sub.B, independently of one another, are selected from the group consisting of H or an hydroxyalkyl- or thiol-substituted alkyl group having from 1 to 6 carbon atoms;
- R.sub.i and R.sub.x+1, independently of one another, are selected from the group consisting of alkyl groups having from 1 to about 6 carbon atoms;
- Y.sub.c.sup.- is an anion where c is the number of positive charges in the compound divided by the valency of the anion;
- and
- A.sub.i and A.sub.x+1, independently of one another, are selected from the group of straight chain or branched alkyl, alkenyl or alkynyl groups having from 6 to about 22 carbon atoms.
A kit for preparing a lipid aggregate comprising the polycation lipid of formula ##STR12## wherein x is an integer from 1 to about 20;
- n.sub.i, where i=1 to x, independently of one another, are integers varying from 1 to about 6;
- R.sub.A and R.sub.B, independently of one another, are selected from the group consisting of H or an alkyl, hydroxyalkyl- or thiol-substituted alkyl group having from 1 to 6 carbon atoms;
- R.sub.i and R.sub.x+1, independently of one another, are selected from the group consisting of alkyl groups having from 1 to about 6 carbon atoms;
- Y.sub.c.sup.- is an anion where c is the number of positive charges in the compound divided by the valency of the anion;
- and
- A.sub.i and A.sub.x+1, independently of one another, are selected from the group of straight chain or branched alkyl, alkenyl or alkynyl groups having from 6 to about 22 carbon atoms.
Dependencies are inferred from the claim text.