Invitrogen Corporation

Life Technologies Corporation

Malek Masoud

Gulilat Gebeyehu

Yongliang Chu

Disclosed are compounds capable of facilitating transport of biologically active agents or substances into cells having the general structure: wherein Q is selected from the group consisting of N, O and S; L is any bivalent organic radical capable of linking each Q, such as C, CH, (CH), or {(CH)&#x2014;Y&#x2014;(CH)}, wherein Y is selected from the group consisting of CH, an ether, a polyether, an amide, a polyamide, an ester, a sulfide, a urea, a thiourea, a guanidyl, a carbamoyl, a carbonate, a phosphate, a sulfate, a sulfoxide, an imine, a carbonyl, and a secondary amino group and wherein Y is optionally substituted by &#x2014;X-L'-X&#x2014;Z or &#x2014;Z; RR, independently of one another, are selected from the group consisting of H, &#x2014;(CH)-D-Z, an alkyl, an alkenyl, an aryl, and an alkyl or alkyl ether optionally substituted by one or more of an alcohol, an aminoalcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, an alkylthio, a urea, a thiourea, a guanidyl, or a carbamoyl group, and wherein at least one of R, R, Rand Ris a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group; and anyone of R, R, Rand/or Rmay optionally be covalently linked with each other, with Y or with L when L is C or CH to form a cyclic moiety; Z is selected from the group consisting of amine, spermiyl, carboxyspermiyl, guanidyl, spermidinyl, putricinyl, diaminoalkyl, pyridyl, piperidinyl, pyrrolidinyl, polyamine, amino acid, peptide, and protein; Xand X, independently of one another, are selected from the group consisting of NH, O, S, alkylene, and arylene; L&#x2032; is selected from the group consisting of alkylene, alkenylene, alkynylene, arylene, alkylene ether, and polyether; D is Q or a bond; Aand A, independently of one another, are selected from the group consisting of CHO, CHS, CHNH, C(O), C(NH), C(S) and (CH)t; X is a physiologically acceptable anion; m, n, r, s, u, v, w and y are 0 or 1, with the proviso that when both m and n are 0 at least one of r, s, u and y is other than 0; i, j, k, l, p and are integers from 0 to about 100; q is an integer from 1 to about 1000; and a is the number of positive charge divided by the valence of the anion.

Transfection reagents

Disclosed are cationic lipid compounds and compositions of lipid aggregates for delivery of macromolecules and other compounds into cells. The compounds can be used alone or in combination with other compounds to prepare liposomes and other lipid aggregates suitable for transfection or delivery of compounds to target cells, either in vitro or in vivo. The compounds are preferably polycationic and preferably form highly stable complexes with various anionic macromolecules, particularly polyanions such as nucleic acids. These compounds have the property, when dispersed in water, of forming lipid aggregates which associate strongly, via their cationic portion, with polyanions. Also disclosed are intermediates for preparing the compound and compositions of the invention and methods of using the compounds to introduce other compounds into cells.

Disclosed are cationic lipid compounds and compositions of lipid aggregates for delivery of macromolecules and other compounds into cells. The compounds can be used alone or in combination with other compounds lo prepare liposomes and other lipid aggregates suitable for iransfcclion or delivery of compounds to target cells, cither in vitro or in vivo. The compounds are preferably polycationic and preferably form highly stable complexes with various anionic macromolecules. particularly polyanions such as nucleic acids. These compounds have the properly, when dispersed in water, of forming lipid aggregates which associate strongly, via their cationic portion, with polyanions. Also disclosed are intermediates for preparing the compound and compositions of the invention and methods of using the compounds to introduce other compounds into cells.

Disclosed are compounds capable of facilitating transport of biologically active agents or substances into cells having the general structure: wherein Q is selected from the group consisting of N, O and S; L is any bivalent organic radical capable of linking each Q, such as C, CH, (CH)l, or {(CH)i-Y&#x2014;(CH)j}k, wherein Y is selected from the group consisting of CH, an ether, a polyether, an amide, a polyamide, an ester, a sulfide, a urea, a thiourea, a guanidyl, a carbamoyl, a carbonate, a phosphate, a sulfate, a sulfoxide, an imine, a carbonyl, and a secondary amino group and wherein Y is optionally substituted by &#x2014;X-L'-X-Z or -Z; R-R, independently of one another, are selected from the group consisting of H, &#x2014;(CH)p-D-Z, an alkyl, an alkenyl, an aryl, and an alkyl or alkyl ether optionally substituted by one or more of an alcohol, an aminoalcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, an alkylthio, a urea, a thiourea, a guanidyl, or a carbamoyl group, and wherein at least one of R, R, Rand Ris a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group; and anyone of R, R, Rand/or Rmay optionally be covalently linked with each other, with Y or with L when L is C or CH to form a cyclic moiety; Z is selected from the group consisting of amine, spermiyl, carboxyspermiyl, guanidyl, spermidinyl, putricinyl, diaminoalkyl, pyridyl, piperidinyl, pyrrolidinyl, polyamine, amino acid, peptide, and protein; Xand X, independently of one another, are selected from the group consisting of NH, O, S, alkylene, and arylene; L&#x2032; is selected from the group consisting of alkylene, alkenylene, alkynylene, arylene, alkylene ether, and polyether; D is Q or a bond; Aand A, independently of one another, are selected from the group consisting of CHO, CHS, CHNH, C(O), C{NH), C(S) and (CH)t; X is a physiologically acceptable anion; m, n, r, s, u, v, w and y are 0 or 1, with the proviso that when both m and n are 0 at least one of r, s, u and y is other than 0; i, j, k, l, p and are integers from 0 to about 100; q is an integer from 1 to about 1000; and a is the number of positive charge divided by the valence of the anion.

Disclosed are compounds capable of facilitating transport of biologically active agents or substances into cells having the general structure: wherein Q is selected from the group consisting of N, O and S; L is any bivalent organic radical capable of linking each Q, such as C, CH, (CH)l, or {(CH)i&#x2014;Y&#x2014;(CH)j}k, wherein Y is selected from the group consisting of CH, an ether, a polyether, an amide, a polyamide, an ester, a sulfide, a urea, a thiourea, a guanidyl, a carbamoyl, a carbonate, a phosphate, a sulfate, a sulfoxide, an imine, a carbonyl, and a secondary amino group and wherein Y is optionally substituted by &#x2014;X&#x2014;L'&#x2014;X&#x2014;Z or &#x2014;Z; R&#x2014;R, independently of one another, are selected from the group consisting of H, &#x2014;(CH)p-D-Z, an alkyl, an alkenyl, an aryl, and an alkyl or alkyl ether optionally substituted by one or more of an alcohol, an aminoalcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, an alkylthio, a urea, a thiourea, a guanidyl, or a carbamoyl group, and wherein at least one of R, R, Rand Ris a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group; and anyone of R, R, Rand/or Rmay optionally be covalently linked with each other, with Y or with L when L is C or CH to form a cyclic moiety; Z is selected from the group consisting of amine, spermiyl, carboxyspermiyl, guanidyl, spermidinyl, putricinyl, diaminoalkyl, pyridyl, piperidinyl, pyrrolidinyl, polyamine, amino acid, peptide, and protein; Xand X, independently of one another, are selected from the group consisting of NH, O, S, alkylene, and arylene; L&#x2032; is selected from the group consisting of alkylene, alkenylene, alkynylene, arylene, alkylene ether, and polyether; D is Q or a bond; Aand A, independently of one another, are selected from the group consisting of CHO, CHS, CHNH, C(O), C{NH), C(S) and (CH)t; X is a physiologically acceptable anion; m, n, r, s, u, v, w and y are 0 or 1, with the proviso that when both m and n are 0 at least one of r, s, u and y is other than 0; i, j, k, l, p and are integers from 0 to about 100; q is an integer from 1 to about 1000; and a is the number of positive charge divided by the valence of the anion.

Disclosed are compounds capable of facilitating transport of biologically active agents or substances into cells having the general structure: wherein Q is selected from the group consisting of N, O and S; L is any bivalent organic radical capable of linking each Q, such as C, CH, (CH)I, or {(CH)i-Y&#x2014;(CH)j}k, wherein Y is selected from the group consisting of CH, an ether, a polyether, an amide, a polyamide, an ester, a sulfide, a urea, a thiourea, a guanidyl, a carbamoyl, a carbonate, a phosphate, a sulfate, a sulfoxide, an imine, a carbonyl, and a secondary amino group and wherein Y is optionally substituted by &#x2014;X-L'-X-Z or -Z; R-R, independently of one another, are selected from the group consisting of H, &#x2014;(CH)p-D-Z, an alkyl, an alkenyl, an aryl, and an alkyl or alkyl ether optionally substituted by one or more of an alcohol, an aminoalcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, an alkylthio, a urea, a thiourea, a guanidyl, or a carbamoyl group, and wherein at least one of R, R, Rand Ris a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group; and anyone of R, R, Rand/or Rmay optionally be covalently linked with each other, with Y or with L when L is C or CH to form a cyclic moiety; Z is selected from the group consisting of amine, spermiyl, carboxyspermiyl, guanidyl, spermidinyl, putricinyl, diaminoalkyl, pyridyl, piperidinyl, pyrrolidinyl, polyamine, amino acid, peptide, and protein; Xand X, independently of one another, are selected from the group consisting of NH, O, S, alkylene, and arylene; L&#x2032; is selected from the group consisting of alkylene, alkenylene, alkynylene, arylene, alkylene ether, and polyether; D is Q or a bond; Aand A, independently of one another, are selected from the group consisting of CHO, CHS, CHNH, C(O), C{NH), C(S) and (CH)t; X is a physiologically acceptable anion; m, n, r, s, u, v, w and y are 0 or 1, with the proviso that when both m and n are 0 at least one of r, s, u and y is other than 0; i, j, k, l, p and are integers from 0 to about 100; q is an integer from 1 to about 1000; and a is the number of positive charge divided by the valence of the anion.

Disclosed are compounds capable of facilitating transport of biologically active agents or substances into cells having the general structure: wherein

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Gaithersburg, MD, United States of America

Malek Masoud