Polymers containing enzymatically degradable bonds, 9. Chymotrypsm catalyzed hydrolysis of a p‐nitroanilide drug model, p bound via oligopeptides onto poly(vinylpyrrolidone‐co‐maleic anhydride)

Pató, János; Azori, M.; Ulbrich, Karel; Kopeček, Jindřich

doi:10.1002/macp.1984.021850201

Cited by 25 publications

(12 citation statements)

References 30 publications

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“…PVP oligomers terminated with ester groups are intermediates for the preparation of end-carboxylated PVP amenable to coupling reactions with hydroxylated or aminated compounds. For instance, they may be used for grafting proteins 2) and for preparing oligomeric prodrugs 7) , as well as PVP-grafted polysaccharides and other hydroxylated natural polymers.…”

Section: Discussionmentioning

confidence: 99%

“…However, in contrast to proteins, PVP is physiologically inactive which has led to its use as a blood plasma substitute or blood volume expander 5) , although these applications are now very much restricted since it is not metabolized or in any way degraded in the body. Moreover, PVP was the first synthetic polymer to be used for the modification of therapeutically useful enzymes 6) and it has been proposed as a soluble drug carrier 7,8) .…”

Section: Introductionmentioning

confidence: 99%

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New ester and lactone end-functionalized N-vinyl-2-pyrrolidinone oligomers

Ranucci

Tarabić

Gilberti³

et al. 2000

Macromol. Chem. Phys.

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New oligomers of N‐vinyl‐2‐pyrrolidinone functionalized at one end with either ester or lactone functions were obtained by radical polymerization in the presence of different ester (methyl isobutyrate and methyl phenylacetate) and lactone (ε‐caprolactone, δ‐valerolactone and γ‐butyrolactone) compounds as chain transfer agents. The oligomeric samples obtained were characterized in terms of molecular weight and molecular weight distribution by means of analytical size exclusion chromatography (SEC), using purposely synthesized poly(N‐vinyl‐2‐pyrrolidinone) standards. The chain transfer constant CT of either methyl isobutyrate, δ‐valerolactone, or γ‐butyrolactone towards N‐vinyl‐2‐pyrrolidinone were determined with the help of the known cumulative number‐average degree of polymerization Xn and monomer conversion Yt of the samples during the reaction.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

New ester and lactone end-functionalized N-vinyl-2-pyrrolidinone oligomers

Ranucci

Tarabić

Gilberti³

et al. 2000

Macromol. Chem. Phys.

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“…6,27 This was attributed to the higher steric hindrance for the access of the enzyme to the oligopeptide substrate in high MW polymers. 28 Another point to be considered is the MW threshold for the elimination of macromolecules via glomerular filtration, which is ϳ 50 kDa.…”

Section: Oligo(bis-tyrhcl-peg 6 Kda-sebacate) (Oligomerization)mentioning

confidence: 97%

Enzymatically degradable prodrugs: A novel methodology for drug linkage

Padmaja

Lele

Deshpande

et al. 2002

J of Applied Polymer Sci

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ABSTRACT:We have synthesized a novel enzymatically degradable prodrug system based on poly(ethylene glycol) (PEG) and tyrosine units by employing a synthetic methodology which eliminated the use of conventional blocking and deblocking methodology used for chemical linkage of drug molecule to the pendant -NH 2 group of amino acid. A diester of PEG (6 kDa) and tyrosine hydrochloride was synthesized by dicyclohexyl carbodiimide (DCC)-mediated condensation. In the second stage, oligomers were prepared by condensing phenolic -OH groups of tyrosine in the diester with sebacic acid, using DCC. Finally, the hydrochloride salt of tyrosine in the oligomer was treated with triethylamine to activate -NH 2 groups, which were reacted with benzoyl chloride to obtain a model prodrug system. The products synthesized were characterized by IR, 1 H-NMR, and GPC. The spectral data were in accordance with the proposed structures of products. Chymotrypsin-catalyzed degradation of the oligomers was characterized by both MW measurements and Ninhydrin assay for free tyrosine. Degradation studies indicated that the rate of main-chain degradation (ester hydrolysis) is higher than that of the side chain (amide hydrolysis). This new, simple methodology should be useful for conjugating a variety of bioactive molecules to enzymatically degradable PEG-amino acid based polymers.

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“…PVP has also been proposed for the modification of therapeutically useful enzymes [21] and as a soluble drug carrier. [22,23] Communication: x-Hydroxy-functionalized oligo(Nvinyl-2-pyrrolidinone) (PVPOH) was prepared by chaintransfer radical polymerization in the presence of 2-isopropoxyethanol as the chain-transfer agent, and grafted onto dextran. Two PVP-Dex graft copolymers were obtained starting from different PVPOH/dextran weight ratios in the feed, namely 2 : 1 and 5 : 1.…”

Section: Introductionmentioning

confidence: 99%

“…[24 -27] The synthetic method applied was the radical polymerization of VP in the presence of functionalized chain-transfer agents (CTA) with small chain-transfer constants, thus facilitating molecular weight control. [21,22] Using this technique, both x-hydroxy-, x-lactone-and x-ester-functionalized VP oligomers were prepared. These VP oligomers are endowed with wide synthetic potential, e. g. in the synthesis of graft-copolymers.…”

Section: Introductionmentioning

confidence: 99%