Prev. Article Next Article Table of Contents

Article

Design, Synthesis, and in Vitro Gene Delivery Efficacies of Novel Cholesterol-Based Gemini Cationic Lipids and Their Serum Compatibility: A Structure−Activity Investigation

Supporting Info

Avinash Bajaj,^† Paturu Kondiah,^‡ and Santanu Bhattacharya*^†^§

Department of Organic Chemistry, Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore 560 012, India, and Chemical Biology Unit of JNCASR, Bangalore 560 064, India

J. Med. Chem., 2007, 50 (10), pp 2432–2442

DOI: 10.1021/jm0611253

Publication Date (Web): April 20, 2007

†

Department of Organic Chemistry, Indian Institute of Science.

‡

Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science.

Corresponding author. Phone: (91)-80-2293-2664. Fax: (91)-80-2360-0529. E-mail: sb@orgchem.iisc.ernet.in.

JNCASR.

Abstract

Five cholesterol-based gemini cationic lipids, which differ in the length of the spacer [−(CH₂)_n−] chain between the head groups, have been synthesized. These lipids are useful as nonviral gene delivery agents, and all cholesterol-based gemini lipids (2a−2e) are better transfecting agents than their monomeric lipid counterpart 1. Transfection efficiency of all the gemini lipids except lipid 2a [−(CH₂)₃−] was maintained even when the serum was present during the transfection conditions as compared to the monomeric lipid 1, with which a dramatic decrease in transfection efficiency was observed. With the increase in spacer chain length from propanediyl [−(CH₂)₃−] to pentanediyl [−(CH₂)₅−], transfection efficiency increased both in the absence and presence of serum. However, transfection efficiency decreased with further increase in the length from the pentanediyl [−(CH₂)₅−] to the dodecanediyl [−(CH₂)₁₂−] spacer. Among these gemini lipids 2c showed the highest transfection activity, which was also greater than that of the commercially available formulation.

View: Full Text HTML | Hi-Res PDF

Tools

SciFinder Links

History

Published In Issue May 17, 2007
Received September 28, 2006

Recommend & Share

Related Content

Synthesis and Gene Transfer Activities of Novel Serum Compatible Cholesterol-Based Gemini Lipids Possessing Oxyethylene-Type SpacersBioconjugate Chemistry
- Synthesis and Gene Transfer Activities of Novel Serum Compatible Cholesterol-Based Gemini Lipids Possessing Oxyethylene-Type Spacers
  Avinash Bajaj, Paturu Kondaiah, and Santanu Bhattacharya
  Bioconjugate Chemistry 2007 18 (5), pp 1537–1546
  Abstract: Four novel cholesterol-based gemini cationic lipids differing in the length of oxyethylene-type spacers [−CH₂−(CH₂−O−CH₂)_n−CH₂−] between each ammonium headgroup have been synthesized. These formed stable suspensions in aqueous media. Cationic liposomes ...
  Abstract | Full Text HTML | Hi-Res PDF
Structure−Function Correlation of Chloroquine and Analogues as Transgene Expression Enhancers in Nonviral Gene DeliveryJournal of Medicinal Chemistry
- Structure−Function Correlation of Chloroquine and Analogues as Transgene Expression Enhancers in Nonviral Gene Delivery
  Jianjun Cheng, Ryan Zeidan, Swaroop Mishra, Aijie Liu, Suzie H. Pun, Rajan P. Kulkarni, Gregory S. Jensen, Nathalie C. Bellocq, and Mark E. Davis
  Journal of Medicinal Chemistry 2006 49 (22), pp 6522–6531
  Abstract: To understand how chloroquine (CQ) enhances transgene expression in polycation-based, nonviral gene delivery systems, a number of CQ analogues with variations in the aliphatic amino side chain or in the aromatic ring are synthesized and investigated. Our ...
  Abstract | Full Text HTML | Hi-Res PDF
Distance of Hydroxyl Functionality from the Quaternized Center Influence DNA Binding and in Vitro Gene Delivery Efficacies of Cationic Lipids with Hydroxyalkyl HeadgroupsJournal of Medicinal Chemistry
- Distance of Hydroxyl Functionality from the Quaternized Center Influence DNA Binding and in Vitro Gene Delivery Efficacies of Cationic Lipids with Hydroxyalkyl Headgroups
  Yenugonda Venkata Mahidhar, Mukthavaram Rajesh, Sunkara Sakunthala Madhavendra, and Arabinda Chaudhuri
  Journal of Medicinal Chemistry 2004 47 (23), pp 5721–5728
  Abstract: In vitro gene delivery efficacies of cationic amphiphiles 1−7 (Scheme 1) were measured by both the reporter gene expression assays in CHO, COS-1, HepG2, and MCF7 cells and by the whole cell histochemical X-gal staining of representative Chinese hamster ...
  Abstract | Full Text HTML | Hi-Res PDF

Article

Design, Synthesis, and in Vitro Gene Delivery Efficacies of Novel Cholesterol-Based Gemini Cationic Lipids and Their Serum Compatibility: A Structure−Activity Investigation

Abstract

Tools

SciFinder Links

History

Recommend & Share

Related Content

Synthesis and Gene Transfer Activities of Novel Serum Compatible Cholesterol-Based Gemini Lipids Possessing Oxyethylene-Type Spacers

Structure−Function Correlation of Chloroquine and Analogues as Transgene Expression Enhancers in Nonviral Gene Delivery

Distance of Hydroxyl Functionality from the Quaternized Center Influence DNA Binding and in Vitro Gene Delivery Efficacies of Cationic Lipids with Hydroxyalkyl Headgroups

Other ACS content by these authors:

JOURNALS

BOOKS

MAGAZINE

COMMUNITIES

DIRECTORIES & DATABASES