Delivery of DNA and siRNA by novel gemini-like amphiphilic peptides

被引：42

作者：

Damen, Mark ^{[1
]}

Aarbiou, Jamil ^{[2
]}

van Dongen, Stijn F. M. ^{[2
]}

Buijs-Offerman, Ruvalic M. ^{[2
]}

Spijkers, Patricia P. ^{[2
]}

van den Heuvel, Maaike ^{[1
]}

Kvashnina, Kristina ^{[3
]}

Nolte, Roeland J. M. ^{[1
]}

Scholte, Bob J. ^{[2
]}

Feiters, Martin C. ^{[1
]}

机构：

[1] Radboud Univ Nijmegen, Inst Mol & Mat, Fac Sci, Dept Organ Chem, NL-6525 AJ Nijmegen, Netherlands

[2] Erasmus MC, Dept Cell Biol, NL-3000 CA Rotterdam, Netherlands

[3] ESRF, Netherlands Org Sci Res NWO, DUBBLE CRG, F-38043 Grenoble, France

来源：

JOURNAL OF CONTROLLED RELEASE | 2010年 / 145卷 / 01期

基金：

荷兰研究理事会;

关键词：

Gene transfection; RNA interference; Lipoplex; Lipopeptide; Geminoid; CELL-MEMBRANE DISRUPTION; SOLID-PHASE SYNTHESIS; GENE DELIVERY; NUCLEOCAPSID PROTEIN; SURFACTANTS; PH; PHOSPHORYLATION; LOCALIZATION; TRANSITION; MESSENGER;

D O I：

10.1016/j.jconrel.2010.03.028

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

We report the design, synthesis, and characterization of a novel type of cationic lipopeptide, gemini-like amphiphilic peptides or 'geminoids'. As an example, the SPKR peptide, inspired by biological nucleic acid binding motifs, was appended with unsaturated (oleoyl/oleyl) alkyl tails. The compound shows remarkable DNA and siRNA delivery, without lysogenic helper lipid, in a variety of cells, with a moderate cytotoxic effect. It aggregates to nanoparticles that combine with DNA to lipoplexes, which undergo a change from lamellar to the more lysogenic hexagonal packing upon lowering the pH. The versatility of the chemical approach allowed us to study peptides related to SPKR, and to establish that the Pro and at least one of the cationic (Lys, Arg) residues are essential for the biological activity. (C) 2010 Elsevier B.V. All rights reserved.

引用

页码：33 / 39

页数：7

共 46 条

[1] Backbone amide linker (BAL) strategy for Nα-9-fluorenylmethoxycarbonyl (Fmoc) solid-phase synthesis of unprotected peptide p-nitroanilides and thioesters [J].

Alsina, J ;

Yokum, TS ;

Albericio, F ;

Barany, G .

JOURNAL OF ORGANIC CHEMISTRY, 1999, 64 (24) :8761-8769

[2] PROSPECTS FOR HUMAN-GENE THERAPY [J].

ANDERSON, WF .

SCIENCE, 1984, 226 (4673) :401-409

[3] Transfection mediated by gemini surfactants: Engineered escape from the endosomal compartment [J].

Bell, PC ;

Bergsma, M ;

Dolbnya, IP ;

Bras, W ;

Stuart, MCA ;

Rowan, AE ;

Feiters, MC ;

Engberts, JBFN .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2003, 125 (06) :1551-1558

[4] A large-scale RNAi screen in human cells identifies new components of the p53 pathway [J].

Berns, K ;

Hijmans, EM ;

Mullenders, J ;

Brummelkamp, TR ;

Velds, A ;

Heimerikx, M ;

Kerkhoven, RM ;

Madiredjo, M ;

Nijkamp, W ;

Weigelt, B ;

Agami, R ;

Ge, W ;

Cavet, G ;

Linsley, PS ;

Beijersbergen, RL ;

Bernards, R .

NATURE, 2004, 428 (6981) :431-437

[5] Efficient transfection of DNA by liposomes formulated with cationic gemini amphiphiles [J].

Bombelli, C ;

Faggioli, F ;

Luciani, P ;

Mancini, G ;

Sacco, MG .

JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (16) :5378-5382

[6] The Dutch-Belgian beamline at the ESRF [J].

Borsboom, M ;

Bras, W ;

Cerjak, I ;

Detollenaere, D ;

van Loon, DG ;

Goedtkindt, P ;

Konijnenburg, M ;

Lassing, P ;

Levine, YK ;

Munneke, B ;

Oversluizen, M ;

van Tol, R ;

Vlieg, E .

JOURNAL OF SYNCHROTRON RADIATION, 1998, 5 :518-520

[7] An SAXS/WAXS beamline at the ESRF and future experiments [J].

Bras, W .

JOURNAL OF MACROMOLECULAR SCIENCE-PHYSICS, 1998, B37 (04) :557-565

[8]

Buynsters P. J. J. A., 2002, EUR J ORG CHEM, P1397

[9] Phosphorylation and subcellular localization of transmissible gastroenteritis virus nucleocapsid protein in infected cells [J].

Calvo, E ;

Escors, D ;

López, JA ;

González, JM ;

Alvarez, A ;

Arza, E ;

Enjuanes, L .

JOURNAL OF GENERAL VIROLOGY, 2005, 86 :2255-2267

[10]

Chan W., 1999, Fmoc solid phase peptide synthesis: a practical approach

← 1 2 3 4 5 →