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US 6,110,916 AGranted
Highly packed polycationic ammonium, sulfonium and phosphonium lipids
AssigneeLife Technologies Corporation
InventorsAlberto Haces, Valentina C. Ciccarone
Life of this patent
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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.
Claims57
A compound having the formula:
- and salts thereof where:
- X is N;
- x is an integer ranging from 1 to about 20;
- n.sub.i, where i-1 to x, independently of one another, are integers that can have a value ranging from 1 to about 6;
- r is 0 or 1 with N positively charged when r is 1;
- R.sub.A and R.sub.B, independently or one another, are selected from the group consisting of H, an alkyl, hydroxyalkyl and thiol-substituted alkyl group having from 1 to 6 carbon atoms except that when x=1, R.sub.A and R.sub.B are not hydrogens;
- R.sub.1 and R.sub.2, independently of other R.sub.1 and R.sub.2, are selected from the group consisting of alkyl groups having from 1 to about 6 carbon atoms;
- A.sub.1, independently of other A.sub.1 groups, and A.sub.2 are selected from the group consisting of the groups:
- (a) a straight-chain or branched alkyl, alkenyl, or alkynyl group having from 2 to about 22 carbon atoms wherein one or more non-neighboring --CH.sub.2 -- groups can be replaced with an O or S atom;
- (b) a straight-chain or branched alkyl group substituted with one or two OH, SH, NH.sub.2 or amine groups within about 3 carbon atoms of the bond between A.sub.1 or A.sub.2 and N;
- (c) a substituted straight-chain or branched alkyl, alkenyl or alkynyl group having from 2 to about 22 carbon atoms wherein the substituent is an aromatic, alicyclic heterocyclic or polycyclic ring and wherein one or more of the non-neighboring --CH.sub.2 -- groups of said alkyl, alkenyl or alkynyl group can be substituted with an O or S atom;
- (d) a-B-L group where B is selected from the group consisting of --CO--, --CO.sub.2 --, --O--C--O--, --CO--NH--, --O--CO--NH--, --O--CH.sub.2 --, --S--CH.sub.2 --, --CH.sub.2 --S--, and --CH.sub.2 -- and L is selected from the group consisting of those groups defined in (a) or (c), above, an aromatic, alicyclic, heterocyclic, and a polycyclic ring moiety;
- or
- (e) a --CH(D-L).sub.2 or a --C(D-L).sub.3 group where D is selected from the group --CO--, --CO.sub.2 --, --OCO--, --CO--NH--, --O--CO--NH--, --O--, and --S-- and L is selected from the group consisting of those groups defined in (a) or (c), above, an aromatic, alicyclic, heterocyclic, and a polycyclic ring moiety and
- wherein two A.sub.1 groups or an A.sub.1 and an A.sub.2 group are covalently linked with one another to form a cyclic moiety.
12 more elements
A compound having the formula:
- ##STR9## and salts thereof wherein X is N;
- x is an integer from 1 to 10;
- l, m, and n, independently of one another, are integers ranging in volume from 1 to about 6;
- r is 0 or 1 with N positively charged when r is 1;
- R.sub.A and R.sub.B, independently of one another, are selected from the group consisting of H, an alkyl, hydroxyalkyl, and a thiol-substituted alkyl group having from 1 to 6 carbon atoms;
- R.sub.1 -R.sub.4, independently of one another, are selected from the group of alkyl groups having from 1 to about 6 carbon atoms;
- A.sub.1 -A.sub.3, independently of other A.sub.1 -A.sub.3 groups and A.sub.4 are selected from the group consisting of
- (a) a straight-chain or branched alkyl, alkenyl, or alkynyl group having from 2 to about 22 carbon atoms wherein one or more non-neighboring --CH.sub.2 -- groups can be replaced with an O or S atom;
- (b) a straight-chain or branched alkyl group substituted with one or two OH, SH, NH.sub.2 or amine groups within about 3 carbon atoms of the bond between A.sub.1 or A.sub.2 and N;
- (c) a substituted straight-chain or branched alkyl, alkenyl or alkynyl group having from 2 to about 22 carbon atoms wherein the substituent is an aromatic, alicyclic heterocyclic or polycyclic ring and wherein one or more of the non-neighboring --CH.sub.2 -- groups of said alkyl, alkenyl or alkynyl group can be substituted with an O or S atom;
- (d) a-B-L group where B is selected from the group consisting of --CO--, --CO.sub.2 --, --OCO--, --CO--NH--, --O--CO--NH--, --O--CH.sub.2 --, --S--CH.sub.2 --, --CH.sub.2 --S--, and --CH.sub.2 -- and L is selected from the group consisting of those groups defined in (a) or (c), above, an aromatic, alicyclic, heterocyclic, polycyclic ring moiety;
- and
- (e) a --CH(D-L).sub.2 or a --C(D-L).sub.3 group where D is selected from the group consisting of --CO--, --CO.sub.2 --, --OCO--, --CO--NH--, --O--CO--NH--, --O--, and --S-- and L is selected from the group consisting of those groups defined in (a) or (c), above, an aromatic, alicyclic, heterocyclic, and a polycyclic ring moiety and
- wherein at least two of the A.sub.1 -A.sub.4 groups are covalently linked to form a cyclic moiety.
11 more elements
Dependencies are inferred from the claim text.