Novel macrocyclic and acyclic cationic lipids for gene transfer: Synthesis and in vitro evaluation

W. P. D. Goldring; E. Jubeli; R. A. Downs; A. J. S. Johnston; N. A. Khalique; L. Raju; D. Wafadari; M. D. Pungente

doi:10.1016/j.bmcl.2012.05.080

Novel macrocyclic and acyclic cationic lipids for gene transfer: Synthesis and in vitro evaluation

W. P. D. Goldring, E. Jubeli, R. A. Downs, A. J. S. Johnston, N. A. Khalique, L. Raju, D. Wafadari, M. D. Pungente

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Abstract

The synthesis and in vitro evaluation of four cationic lipid gene delivery vectors, characterized by acyclic or macrocyclic, and saturated or unsaturated hydrophobic regions, is described. The synthesis employed standard protocols, including ring-closing metathesis for macrocyclic lipid construction. All lipoplexes studied, formulated from plasmid DNA and a liposome composed of a synthesized lipid, 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine (EPC), and either 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or cholesterol as co-lipid, exhibited plasmid DNA binding and protection from DNase I degradation, and concentration dependent cytotoxicity using Chinese hamster ovary-K1 cells. The transfection efficiency of formulations with cholesterol outperformed those with DOPE, and in many cases the EPC/cholesterol control, and formulations with a macrocyclic lipid (+/− 10:1) outperformed their acyclic counterparts (+/− 3:1).

Originalsprog	Engelsk
Tidsskrift	Bioorganic & Medicinal Chemistry Letters
Vol/bind	22
Udgave nummer	14
Sider (fra-til)	4686-4692
Antal sider	7
ISSN	0960-894X
DOI	https://doi.org/10.1016/j.bmcl.2012.05.080
Status	Udgivet - 2012
Udgivet eksternt	Ja

Link til dokument

10.1016/j.bmcl.2012.05.080

Citer dette

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title = "Novel macrocyclic and acyclic cationic lipids for gene transfer: Synthesis and in vitro evaluation",

abstract = "The synthesis and in vitro evaluation of four cationic lipid gene delivery vectors, characterized by acyclic or macrocyclic, and saturated or unsaturated hydrophobic regions, is described. The synthesis employed standard protocols, including ring-closing metathesis for macrocyclic lipid construction. All lipoplexes studied, formulated from plasmid DNA and a liposome composed of a synthesized lipid, 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine (EPC), and either 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or cholesterol as co-lipid, exhibited plasmid DNA binding and protection from DNase I degradation, and concentration dependent cytotoxicity using Chinese hamster ovary-K1 cells. The transfection efficiency of formulations with cholesterol outperformed those with DOPE, and in many cases the EPC/cholesterol control, and formulations with a macrocyclic lipid (+/− 10:1) outperformed their acyclic counterparts (+/− 3:1).",

author = "Goldring, {W. P. D.} and E. Jubeli and Downs, {R. A.} and Johnston, {A. J. S.} and Khalique, {N. A.} and L. Raju and D. Wafadari and Pungente, {M. D.}",

year = "2012",

doi = "10.1016/j.bmcl.2012.05.080",

language = "English",

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T1 - Novel macrocyclic and acyclic cationic lipids for gene transfer

T2 - Synthesis and in vitro evaluation

AU - Goldring, W. P. D.

AU - Jubeli, E.

AU - Downs, R. A.

AU - Johnston, A. J. S.

AU - Khalique, N. A.

AU - Raju, L.

AU - Wafadari, D.

AU - Pungente, M. D.

PY - 2012

Y1 - 2012

N2 - The synthesis and in vitro evaluation of four cationic lipid gene delivery vectors, characterized by acyclic or macrocyclic, and saturated or unsaturated hydrophobic regions, is described. The synthesis employed standard protocols, including ring-closing metathesis for macrocyclic lipid construction. All lipoplexes studied, formulated from plasmid DNA and a liposome composed of a synthesized lipid, 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine (EPC), and either 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or cholesterol as co-lipid, exhibited plasmid DNA binding and protection from DNase I degradation, and concentration dependent cytotoxicity using Chinese hamster ovary-K1 cells. The transfection efficiency of formulations with cholesterol outperformed those with DOPE, and in many cases the EPC/cholesterol control, and formulations with a macrocyclic lipid (+/− 10:1) outperformed their acyclic counterparts (+/− 3:1).

AB - The synthesis and in vitro evaluation of four cationic lipid gene delivery vectors, characterized by acyclic or macrocyclic, and saturated or unsaturated hydrophobic regions, is described. The synthesis employed standard protocols, including ring-closing metathesis for macrocyclic lipid construction. All lipoplexes studied, formulated from plasmid DNA and a liposome composed of a synthesized lipid, 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine (EPC), and either 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or cholesterol as co-lipid, exhibited plasmid DNA binding and protection from DNase I degradation, and concentration dependent cytotoxicity using Chinese hamster ovary-K1 cells. The transfection efficiency of formulations with cholesterol outperformed those with DOPE, and in many cases the EPC/cholesterol control, and formulations with a macrocyclic lipid (+/− 10:1) outperformed their acyclic counterparts (+/− 3:1).

U2 - 10.1016/j.bmcl.2012.05.080

DO - 10.1016/j.bmcl.2012.05.080

M3 - Journal article

SN - 0960-894X

VL - 22

SP - 4686

EP - 4692

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

IS - 14

ER -