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Design and synthesis of multifunctio...

Seo, Kwang Su.

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Design and synthesis of multifunctional poly(ethylene glycol)s using enzymatic catalysis for multivalent cancer drug delivery.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Design and synthesis of multifunctional poly(ethylene glycol)s using enzymatic catalysis for multivalent cancer drug delivery./
Author:	Seo, Kwang Su.
Description:	234 p.
Notes:	Source: Dissertation Abstracts International, Volume: 73-11(E), Section: B.
Contained By:	Dissertation Abstracts International73-11B(E).
Subject:	Chemistry, Polymer. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3516047
ISBN:	9781267440099

Design and synthesis of multifunctional poly(ethylene glycol)s using enzymatic catalysis for multivalent cancer drug delivery.
Seo, Kwang Su.

Design and synthesis of multifunctional poly(ethylene glycol)s using enzymatic catalysis for multivalent cancer drug delivery. - 234 p.

Source: Dissertation Abstracts International, Volume: 73-11(E), Section: B.

Thesis (Ph.D.)--The University of Akron, 2012.

The objective of this research was to design and synthesize multifunctional poly(ethylene glycol)s (PEG)s using enzyme-catalyzed reactions for multivalent targeted drug delivery. Based on computer simulation for optimum folate binding, a four-arm PEG star topology with Mn = 1000 g/mol was proposed. First, a four-functional core based on tetraethylene glycol (TEG) was designed and synthesized using transesterification and Michael addition reactions in the presence of Candida antarctica lipase B (CALB) as a biocatalyst. The four-functional core (HO)2-TEG-(OH)2 core was successfully prepared by the CALB-catalyzed transesterification of vinyl acrylate (VA) with TEG and then Michael addition of diethanolamine to the resulting TEG diacrylate with/without the use of solvent.

ISBN: 9781267440099Subjects--Topical Terms:

1018428
Chemistry, Polymer.

Design and synthesis of multifunctional poly(ethylene glycol)s using enzymatic catalysis for multivalent cancer drug delivery.
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020 $a 9781267440099
035 $a (MiAaPQ)AAI3516047
035 $a AAI3516047
040 $a MiAaPQ $c MiAaPQ
100 1 $a Seo, Kwang Su. $3 2094123
245 1 0 $a Design and synthesis of multifunctional poly(ethylene glycol)s using enzymatic catalysis for multivalent cancer drug delivery.
300 $a 234 p.
500 $a Source: Dissertation Abstracts International, Volume: 73-11(E), Section: B.
500 $a Adviser: Judit E. Puskas.
502 $a Thesis (Ph.D.)--The University of Akron, 2012.
520 $a The objective of this research was to design and synthesize multifunctional poly(ethylene glycol)s (PEG)s using enzyme-catalyzed reactions for multivalent targeted drug delivery. Based on computer simulation for optimum folate binding, a four-arm PEG star topology with Mn = 1000 g/mol was proposed. First, a four-functional core based on tetraethylene glycol (TEG) was designed and synthesized using transesterification and Michael addition reactions in the presence of Candida antarctica lipase B (CALB) as a biocatalyst. The four-functional core (HO)2-TEG-(OH)2 core was successfully prepared by the CALB-catalyzed transesterification of vinyl acrylate (VA) with TEG and then Michael addition of diethanolamine to the resulting TEG diacrylate with/without the use of solvent.
520 $a The functional PEG arms with fluorescein isothiocyanate (FITC) and folic acid (FA) were prepared using both traditional organic chemistry and enzyme-catalyzed reactions. FITC was reacted with the amine group of H2N-PEG-OH in the presence of triethylamine via nucleophilic addition onto the isothiocyanate group. Then, divinyl adipate (DVA) was transesterified with the FITC-PEG-OH product in the presence of CALB to produce the FITC-PEG vinyl ester that will be attached to the four-functional core via CALC-catalyzed transesterification. For the synthesis of FA-PEG vinyl ester arm, DVA was first reacted with PEG-monobenzyl ether (BzPEG-OH) in bulk in the presence of CALB. The BzPEG vinyl ester was then transesterified with 12-bromo-1-dodecanol in the presence of CALB. Finally, BzPEG-Br was attached to FA exclusively in the gamma position using a new method.
520 $a The thesis also discusses fundamental studies that were carried out in order to get better understanding of enzyme catalyzed transesterification and Michael addition reactions. First, in an effort to investigate the effects of reagent and enzyme concentrations in transesterification, vinyl methacrylate (VMA) was reacted with 2-(hydroxyethyl) acrylate (2HEA) in the presence of CALB. When the reaction was performed in tetrahydrofuran (THF) with a 2HEA concentration of 0.10 mol/L, only 19% conversion was observed within 4 hours, whereas complete conversion was achieved under solventless conditions. The effect of enzyme concentration in reactions with and without solvent was also studied.
520 $a The effect of DVA concentration on the CALB-catalyzed transesterification with TEG was studied under solventless conditions. When 1.5 molar equivalent of DVA per OH in TEG was used, 42% divinyl-functionalized product was observed together with 56.5% oligomerized (di-, tri-, tetra- and pentamer) products. At 10 eq. of DVA, only 18.4% oligomerized products were obtained. The effect of diol molecular weight was also investigated. At 10.0 eq. DVA per OH only 2% dimer was observed with PEG Mn=1000 g/mol, and a single divinyl functionalized product was obtained with M n=2000 g/mol. The effects of polymer molecular weight and DVA concentration were also studied in the reaction of DVA with PEG monomethyl ether (MPEG-OH, Mn=1100 g/mol and 2000 g/mol). The extent of coupling decreased from 35% to 0.4% when the DVA concentration was increased from 1.5 to 10 per -OH in the MPEG-OH. No coupling was observed with MPEG-OH Mn=2000 g/mol at 5 eq. DVA per -OH. Following these fundamental studies, TEGs and PEGs were enzymatically functionalized. TEGs were transesterified with VMA and vinyl crotonate in the presence of CALB under solventless conditions within 4 hours of reaction time. Benzyl protected TEG-OHs were also successfully functionalized with VMA and vinyl crotonate in the presence of CALB under solventless conditions within 2 hours. An eight-functional molecule was also synthesized from (HO)2-TEG-(OH) 2. First an alpha-vinyl-o-acrylate linker was prepared by the transesterification of DVA with 2HEA. This linker was then transesterified with (HO)-TEG-(OH)2, followed by Michael addition of DEA to the tetra-acrylated TEG. (Abstract shortened by UMI.).
590 $a School code: 0003.
650 4 $a Chemistry, Polymer. $3 1018428
650 4 $a Engineering, Materials Science. $3 1017759
690 $a 0495
690 $a 0794
710 2 $a The University of Akron. $b Polymer Science. $3 2094124
773 0 $t Dissertation Abstracts International $g 73-11B(E).
790 $a 0003
791 $a Ph.D.
792 $a 2012
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3516047