发明名称 Lipids for transfection of Eukaryotic cells
摘要 Compositions and methods for improved delivery of macromolecules into eukaryotic cells are provided. Fusogenic peptides from fusion proteins of non-enveloped viruses enhance the efficiency of transfection of eukaryotic cells mediated by transfection agents such as cationic lipids, polycationic polymers such as PEI and dendrimers. These fusogenic peptides are used as part of a transfection complex that efficiently delivers a macromolecule, for example, a nucleic acid, into a eukaryotic cell. Novel cationic lipids and compositions of cationic lipids also are provided that may be used for the introduction of macromolecules such as nucleic acids, proteins and peptides into a variety of cells and tissues. The lipids can be used alone, in combination with other lipids and/or in combination with fusogenic peptides to prepare transfection complexes.
申请公布号 US8759499(B2) 申请公布日期 2014.06.24
申请号 US201113073972 申请日期 2011.03.28
申请人 Molecular Transfer, Inc. 发明人 Jessee Joel;Gebeyehu Gulilat
分类号 C07D487/00;A61K48/00;A61K51/00;A61K36/14;A01N63/00 主分类号 C07D487/00
代理机构 Perkins Coie LLP 代理人 Perkins Coie LLP
主权项 1. A compound having the formula: wherein X1 and X2 independently are selected from the group consisting of (CH2)n, (CHOH)n, and CONH; X5 and X6 independently are (CH2)1-6; W1 and W2 independently are selected from the group consisting of, hydrogen, —OH, —O—(C1-C18) alkyl, —O—(C1-C18) alkenyl, —O—(C1-C18) alkynyl, —NH2, —NH(CH2)sCH3, —N((CH2)sCH3), —SH, and —NH—NH2; R3 and (R6)q independently are selected from the group consisting of N, NH, CH, and N(CH2)sCH3, and q=0-1; R4 and R5 independently are selected from the group consisting of (CH2)n, (CH2—CHOH—CH2)n, (CHOH)n, HNCO, CONH, CO, —O—, —S—, —S—S—, polyamide and an ester linkage; L1 and L2 independently are selected from the group consisting of —NH—, —O—, —NHCO—, —CONH—, —OCO—, —COO—, —CO—, —S—, —S—S—, —NHC(O)O—, —OC(O)NH—, —NHCONH—, —NHC(═NH)NH—, —NH—NH—, —S(O)— and —SO2—; Y is a heterocyclic moiety containing at least one amine or amide moiety, wherein the points of attachment of Y are carbon and/or heteroatoms; R1 and R2 independently are selected from the group consisting of hydrogen, primary alkylamine, secondary alkylamine, tertiary alkyl amine, quaternary alkylamine, alkenylamine, secondary alkenylamine, tertiary alkenyl amine, quaternary alkenylamine, alkynylamine, secondary alkynylamine, tertiary alkynylamine, quaternary alkynylamine amino alcohol, alkyl polyamine, alkenyl polyamine, alkynyl polyamine, spermidine, spermine, carboxy spermine, guanidinium, pyridinium, pyrollidinium, piperidinium, piperazinium, amino acyl, peptidyl, and protein; Z1 and Z2 independently are selected from the group consisting of long chain straight alkyl, long chain branched alkyl, long chain cycloalkyl, long chain straight chain alkenyl, long chain branched alkenyl, long chain cycloalkenyl, long chain straight chain alkynyl, and long chain branched alkynyl, m, n, p, and s independently are 0-6, with the proviso that when m, n, and p all are 0 then Y is eliminated and R3 is bonded directly to X2.
地址 Gaithersburg MD US