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Structural Effects of Carbohydrate-Containing Polycations on Gene Delivery. 3. Cyclodextrin Type and Functionalization

Popielarski, Stephen R. and Mishra, Swaroop and Davis, Mark E. (2003) Structural Effects of Carbohydrate-Containing Polycations on Gene Delivery. 3. Cyclodextrin Type and Functionalization. Bioconjugate Chemistry, 14 (3). pp. 672-678. ISSN 1043-1802. doi:10.1021/bc034010b. https://resolver.caltech.edu/CaltechAUTHORS:20170125-084654389

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Abstract

Linear cationic β-cyclodextrin (β-CD)-based polymers can form polyplexes with plasmid DNA and transfect cultured cells. The effectiveness of the gene delivery and the cellular toxicity has been related to structural features in these polycations. Previous β-CD polycations were prepared from the cocondensation of 6^A,6^D-dideoxy-6^A,6^D-diamino-β-CD monomers with other difunctionalized monomers such as dimethyl suberimidate (DMS). Here, the type of CD and its functionalization are varied by synthesizing numerous 3^A,3^B-dideoxy-3^A,3^B-diamino-β- and γ-CD monomers. Both alkyl- and alkoxydiamines are prepared in order to vary the nature of the spacing between the CD and the primary amines in the monomers. These diamino-CD-monomers are polymerized with DMS to yield amidine-based polycations. The nature of the spacer between the CD-ring and the primary amines of each monomer is found to influence both molecular weight and polydispersity of the polycations. When these polycations are used to form polyplexes with plasmid DNA, longer alkyl regions between the CD and the charge centers in the polycation backbone increase transfection efficiency and toxicity in BHK-21 cells, while increasing hydrophilicity of the spacer (alkoxy versus alkyl) provides for lower toxicity. Further, γ-CD-based polycations are shown to be less toxic than otherwise identical β-CD-based polycations.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/bc034010bDOIArticle
http://pubs.acs.org/doi/abs/10.1021/bc034010bPublisherArticle
http://pubs.acs.org/doi/suppl/10.1021/bc034010bRelated ItemSupporting Information
ORCID:
AuthorORCID
Mishra, Swaroop0000-0002-2665-5385
Davis, Mark E.0000-0001-8294-1477
Additional Information:© 2003 American Chemical Society. Received 21 January 2003. Published online 22 March 2003. Published in print 1 May 2003. S.R.P. thanks the Department of Defense for an NDSEG fellowship. We would also like to thank Insert Therapeutics Inc. for partial support of this project. M.E.D. is a consultant to and has financial interest in Insert Therapeutics, Inc.
Funders:
Funding AgencyGrant Number
National Defense Science and Engineering Graduate (NDSEG) FellowshipUNSPECIFIED
Insert Therapeutics Inc.UNSPECIFIED
Issue or Number:3
DOI:10.1021/bc034010b
Record Number:CaltechAUTHORS:20170125-084654389
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170125-084654389
Official Citation:Structural Effects of Carbohydrate-Containing Polycations on Gene Delivery. 3. Cyclodextrin Type and Functionalization Stephen R. Popielarski, Swaroop Mishra, and Mark E. Davis Bioconjugate Chemistry 2003 14 (3), 672-678 DOI: 10.1021/bc034010b
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:73701
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:25 Jan 2017 20:47
Last Modified:11 Nov 2021 05:20

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