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Oligo-L-lysine-, dextran-, and alkyl...

Steele, Terry William Joseph.

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Oligo-L-lysine-, dextran-, and alkyl- derivatives of polyethylenimine for the development of novel gene transfection vectors.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Oligo-L-lysine-, dextran-, and alkyl- derivatives of polyethylenimine for the development of novel gene transfection vectors./
Author:	Steele, Terry William Joseph.
Description:	244 p.
Notes:	Adviser: W. T. Shier.
Contained By:	Dissertation Abstracts International67-11B.
Subject:	Chemistry, Pharmaceutical. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3243381
ISBN:	9780542993121

Oligo-L-lysine-, dextran-, and alkyl- derivatives of polyethylenimine for the development of novel gene transfection vectors.
Steele, Terry William Joseph.

Oligo-L-lysine-, dextran-, and alkyl- derivatives of polyethylenimine for the development of novel gene transfection vectors. - 244 p.

Adviser: W. T. Shier.

Thesis (Ph.D.)--University of Minnesota, 2006.

Synthesis of a dendrimer for a proposed non-viral vector has been taken with the following attributes: an inner polycationic polyethylenimine (PEI) core (to help lyse endosomes by osmotic effects) linked to a hydrophobic shell (to lyse endocytotic vesicles by lipid depletion) linked to an outer shell of oligoamines (which binds DNA and the cell surface) by means of acid labile linkers designed to be disrupted by changing pH conditions inside the endocytotic vesicle. The synthesis of the proposed dendrimer will take place in a part convergent, part divergent method, to minimize the handling of the acid labile linker. The hydrophobic shell has been added to the PEI core in a divergent mode. This reaction proceeds by alkyl iodide displacement on the PEI amines. The terminal functionality of the alkyl groups consists of a homocysteine thiolactone ring where upon treatment with base reveals a thiol functionality. This thiol reacts readily with homo-bifunctional acid labile maleimide linkers. In the last step, a convergent synthesis approach will be used to couple the PEI-hydrophobic shell to the linker-oligoamine, via a thioether bond. The outer shell will consist of short oligoamines such as spermidine, and low molecular weight polyethylenimine. This oligoamine shell will be attached through acid labile linkers, which will allow detachment of the complexed DNA-Oligoamines once inside the acidic endocytotic environment. The dendrimeric vectors were analyzed using dynamic and static laser light scattering to characterize the vectors and their complexes with plasmid DNA. Flow cytometry was employed to quantify the reporter protein (enhanced green fluorescent protein) and cytotoxicity of the dendrimeric vector/pEGFP complexes. Dextran and oligo-L-lysine polyethylenimine derivatives were also synthesized and characterized in regards to their potential as gene delivery vectors.

ISBN: 9780542993121Subjects--Topical Terms:

550957
Chemistry, Pharmaceutical.

Oligo-L-lysine-, dextran-, and alkyl- derivatives of polyethylenimine for the development of novel gene transfection vectors.
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100 1 $a Steele, Terry William Joseph. $3 1287161
245 1 0 $a Oligo-L-lysine-, dextran-, and alkyl- derivatives of polyethylenimine for the development of novel gene transfection vectors.
300 $a 244 p.
500 $a Adviser: W. T. Shier.
500 $a Source: Dissertation Abstracts International, Volume: 67-11, Section: B, page: 6417.
502 $a Thesis (Ph.D.)--University of Minnesota, 2006.
520 $a Synthesis of a dendrimer for a proposed non-viral vector has been taken with the following attributes: an inner polycationic polyethylenimine (PEI) core (to help lyse endosomes by osmotic effects) linked to a hydrophobic shell (to lyse endocytotic vesicles by lipid depletion) linked to an outer shell of oligoamines (which binds DNA and the cell surface) by means of acid labile linkers designed to be disrupted by changing pH conditions inside the endocytotic vesicle. The synthesis of the proposed dendrimer will take place in a part convergent, part divergent method, to minimize the handling of the acid labile linker. The hydrophobic shell has been added to the PEI core in a divergent mode. This reaction proceeds by alkyl iodide displacement on the PEI amines. The terminal functionality of the alkyl groups consists of a homocysteine thiolactone ring where upon treatment with base reveals a thiol functionality. This thiol reacts readily with homo-bifunctional acid labile maleimide linkers. In the last step, a convergent synthesis approach will be used to couple the PEI-hydrophobic shell to the linker-oligoamine, via a thioether bond. The outer shell will consist of short oligoamines such as spermidine, and low molecular weight polyethylenimine. This oligoamine shell will be attached through acid labile linkers, which will allow detachment of the complexed DNA-Oligoamines once inside the acidic endocytotic environment. The dendrimeric vectors were analyzed using dynamic and static laser light scattering to characterize the vectors and their complexes with plasmid DNA. Flow cytometry was employed to quantify the reporter protein (enhanced green fluorescent protein) and cytotoxicity of the dendrimeric vector/pEGFP complexes. Dextran and oligo-L-lysine polyethylenimine derivatives were also synthesized and characterized in regards to their potential as gene delivery vectors.
590 $a School code: 0130.
650 4 $a Chemistry, Pharmaceutical. $3 550957
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