Publication: Solid phase synthesis of novel asymmetric hydrophilic head cholesterol-based cationic lipids with potential DNA delivery
2
0
Issued Date
2010
Resource Type
File Type
application/pdf
ISSN
9680896
Other identifier(s)
2-s2.0-72149112492
Rights Holder(s)
มหาวิทยาลัยศรีนครินทรวิโรฒ
Bibliographic Citation
Bioorganic and Medicinal Chemistry. Vol 18, No.1 (2010), p.330-342
Suggested Citation
Radchatawedchakoon W., Watanapokasin R., Krajarng A., Yingyongnarongkul B.-E. Solid phase synthesis of novel asymmetric hydrophilic head cholesterol-based cationic lipids with potential DNA delivery. Bioorganic and Medicinal Chemistry. Vol 18, No.1 (2010), p.330-342. doi:10.1016/j.bmc.2009.10.057 Retrieved from: https://hdl.handle.net/20.500.14740/7685
Abstract
Twenty-four asymmetric divalent head group cholesterol-based cationic lipids were designed and synthesized by parallel solid phase chemistry. These asymmetric head groups composed of amino functionality together with trimethylamino, di(2-hydroxyethyl)amino or guanidinyl groups. Spacers between cationic heads and linker were both equal and unequal in length. These lipids were subjected to evaluation for DNA binding affinities by gel retardation assay and were screened for their transfection efficiency on HEK293 cells. Cationic lipids with equal chain length exhibited high transfection efficiency when polar part contained asymmetric polar heads. In contrast, lipids with unequal chain length exhibited high transfection efficiency when polar part contained symmetric heads. According to the optimal formulation, seven lipids exhibited higher transfection efficiency than the commercially available transfection agents, Effectene™, DOTAP and DC-Chol, to deliver DNA into PC3 human prostate adenocarcinoma cells. 3β-[N-(N′-Guanidinyl)-2′-aminoethyl)-N-(2-aminoethyl)ca rbamoyl] cholesterol (5) bearing amino and guanidinyl polar heads exhibited highest transfection efficiency with minimal toxicity. The morphology of active liposomes was observed by transmission electron microscopy (TEM) and size of liposomes were around 200-700 nm. © 2009 Elsevier Ltd. All rights reserved.
Subject(s)
3b [n [n',n' di(2'' hydroxyethyl) 2' aminoethyl] n [n glycine[n (2 aminoethyl)amide]]carbamoyl]cholesterol
3beta [n (2' aminoethyl) n [n glycine[n (2 aminoethyl)amide]]carbamoyl]cholesterol
3beta [n (2' aminoethyl) n [n glycine[n (3 aminopropyl) amide]]carbamoyl]cholesterol
3beta [n (3' aminopropyl) n [n glycine[n (2 aminoethyl) amide]]carbamoyl]cholesterol
3beta [n (3' aminopropyl) n [n glycine[n (3 aminopropyl) amide]]carbamoyl]cholesterol
3beta [n (n' guanidinyl 2' aminoethyl) n [n glycine[n (2 aminoethyl)amide]]carbamoyl]cholesterol
3beta [n (n' guanidinyl 2' aminoethyl) n [n glycine[n (3 aminopropyl)amide]]carbamoyl]cholesterol
3beta [n (n' guanidinyl 3' aminopropyl) n [n glycine [n (3 aminopropyl)amide]]carbamoyl]cholesterol
3beta [n (n' guanidinyl 3' aminopropyl) n [n glycine[n (2 aminoethyl)amide]] carbamoyl]cholesterol
3beta [n (n' guanidinyl) 2' aminoethyl n (2 aminoethyl)carbamoyl]cholesterol
3beta [n (n',n' di(2'' hydroxyethyl) 3' aminopropyl) n (3 aminopropyl)carbamoyl]cholesterol
3beta [n [(n' guanidinyl) 2' aminoethyl] n (2 aminoethyl) carbamoyl]cholesterol
3beta [n [(n' guanidinyl) 3' aminopropyl] n (3 aminoproyl)carbamoyl]cholesterol
3beta [n [(n',n',n' trimethyl) 2' aminoethyl] n (2 amino ethyl)carbamoyl]cholesterol
3beta [n [(n',n',n' trimethyl) 2' aminoethyl] n [n glycine[n (2 aminoethyl)amide]]carbamoyl]cholesterol
3beta [n [(n',n',n' trimethyl) 2' aminoethyl] n [n glycine[n (3 aminopropyl)amide]]carbamoyl]cholesterol
3beta [n [(n',n',n' trimethyl) 3' aminopropyl] n (3 aminopropyl)carbamoyl]cholesterol
3beta [n [(n',n',n' trimethyl) 3' aminopropyl] n [n glycine [n (2 aminoethyl)amide]]carbamoyl]cholesterol
3beta [n [(n',n',n' trimethyl) 3' aminopropyl] n [n glycine [n (3 aminopropyl)amide]]carbamoyl] cholesterol
3beta [n [n',n' di(2'' hydroxyethyl) 2' aminoethyl] n (2 aminoethyl)carbamoyl]cholesterol
3beta [n [n',n' di(2'' hydroxyethyl) 2' aminoethyl] n [n glycine[n (3 aminopropyl)amide]]carbamoyl]cholesterol
3beta [n [n',n' di(2'' hydroxyethyl) 3' aminopropyl] n [n glycine[n (2 aminoethyl)amide]]carbamoyl]cholesterol
3beta [n [n',n' di(2'' hydroxyethyl) 3' aminopropyl] n [n glycine[n (3 aminopropyl)amide]]carbamoyl]cholesterol
3beta [n,n (2,2' diaminoethyl)carbamoyl]cholesterol
3beta [n,n (3,3' diaminopropyl)carbamoyl]cholesterol
Cholesterol derivative
Unclassified drug
Article
Binding affinity
Carbon nuclear magnetic resonance
Controlled study
DNA binding
DNA transfection
Drug design
Drug structure
Drug synthesis
Gene targeting
Human
Human cell
Prostate adenocarcinoma
Proton nuclear magnetic resonance
Solid phase synthesis
Transmission electron microscopy
Binding Sites
Cations
Cell Line
Cell Line, Tumor
Cholesterol
DNA
Humans
Lipids
Liposomes
Phosphatidylethanolamines
Serum
Transfection
3beta [n (2' aminoethyl) n [n glycine[n (2 aminoethyl)amide]]carbamoyl]cholesterol
3beta [n (2' aminoethyl) n [n glycine[n (3 aminopropyl) amide]]carbamoyl]cholesterol
3beta [n (3' aminopropyl) n [n glycine[n (2 aminoethyl) amide]]carbamoyl]cholesterol
3beta [n (3' aminopropyl) n [n glycine[n (3 aminopropyl) amide]]carbamoyl]cholesterol
3beta [n (n' guanidinyl 2' aminoethyl) n [n glycine[n (2 aminoethyl)amide]]carbamoyl]cholesterol
3beta [n (n' guanidinyl 2' aminoethyl) n [n glycine[n (3 aminopropyl)amide]]carbamoyl]cholesterol
3beta [n (n' guanidinyl 3' aminopropyl) n [n glycine [n (3 aminopropyl)amide]]carbamoyl]cholesterol
3beta [n (n' guanidinyl 3' aminopropyl) n [n glycine[n (2 aminoethyl)amide]] carbamoyl]cholesterol
3beta [n (n' guanidinyl) 2' aminoethyl n (2 aminoethyl)carbamoyl]cholesterol
3beta [n (n',n' di(2'' hydroxyethyl) 3' aminopropyl) n (3 aminopropyl)carbamoyl]cholesterol
3beta [n [(n' guanidinyl) 2' aminoethyl] n (2 aminoethyl) carbamoyl]cholesterol
3beta [n [(n' guanidinyl) 3' aminopropyl] n (3 aminoproyl)carbamoyl]cholesterol
3beta [n [(n',n',n' trimethyl) 2' aminoethyl] n (2 amino ethyl)carbamoyl]cholesterol
3beta [n [(n',n',n' trimethyl) 2' aminoethyl] n [n glycine[n (2 aminoethyl)amide]]carbamoyl]cholesterol
3beta [n [(n',n',n' trimethyl) 2' aminoethyl] n [n glycine[n (3 aminopropyl)amide]]carbamoyl]cholesterol
3beta [n [(n',n',n' trimethyl) 3' aminopropyl] n (3 aminopropyl)carbamoyl]cholesterol
3beta [n [(n',n',n' trimethyl) 3' aminopropyl] n [n glycine [n (2 aminoethyl)amide]]carbamoyl]cholesterol
3beta [n [(n',n',n' trimethyl) 3' aminopropyl] n [n glycine [n (3 aminopropyl)amide]]carbamoyl] cholesterol
3beta [n [n',n' di(2'' hydroxyethyl) 2' aminoethyl] n (2 aminoethyl)carbamoyl]cholesterol
3beta [n [n',n' di(2'' hydroxyethyl) 2' aminoethyl] n [n glycine[n (3 aminopropyl)amide]]carbamoyl]cholesterol
3beta [n [n',n' di(2'' hydroxyethyl) 3' aminopropyl] n [n glycine[n (2 aminoethyl)amide]]carbamoyl]cholesterol
3beta [n [n',n' di(2'' hydroxyethyl) 3' aminopropyl] n [n glycine[n (3 aminopropyl)amide]]carbamoyl]cholesterol
3beta [n,n (2,2' diaminoethyl)carbamoyl]cholesterol
3beta [n,n (3,3' diaminopropyl)carbamoyl]cholesterol
Cholesterol derivative
Unclassified drug
Article
Binding affinity
Carbon nuclear magnetic resonance
Controlled study
DNA binding
DNA transfection
Drug design
Drug structure
Drug synthesis
Gene targeting
Human
Human cell
Prostate adenocarcinoma
Proton nuclear magnetic resonance
Solid phase synthesis
Transmission electron microscopy
Binding Sites
Cations
Cell Line
Cell Line, Tumor
Cholesterol
DNA
Humans
Lipids
Liposomes
Phosphatidylethanolamines
Serum
Transfection