2008
DOI: 10.1021/bm701073n
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Polymer Masked−Unmasked Protein Therapy. 1. Bioresponsive Dextrin−Trypsin and −Melanocyte Stimulating Hormone Conjugates Designed for α-Amylase Activation

Abstract: Polymer-protein conjugation, particularly PEGylation, is well-established as a means of increasing circulation time, reducing antigenicity, and improving the stability of protein therapeutics. However, PEG has limitations including lack of polymer biodegradability, and conjugation can diminish or modify protein activity. The aim of this study was to explore a novel approach for polymer-protein modification called polymer-masking-unmasking-protein therapy (PUMPT), the hypothesis being that conjugation of a biod… Show more

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Cited by 90 publications
(108 citation statements)
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“…[5,6] Polymer enzyme liposome therapy (PELT) utilizes a polymer-bound enzyme to trigger the release of drug encapsulated within a liposome. Proof-of-concept studies used N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-Gly-Gly-phospholipase C conjugates to trigger doxorubicin (Doxil ) release from cholesterol-stabilised distearoylphosphatidylcholine liposomes.…”
Section: Introductionmentioning
confidence: 99%
“…[5,6] Polymer enzyme liposome therapy (PELT) utilizes a polymer-bound enzyme to trigger the release of drug encapsulated within a liposome. Proof-of-concept studies used N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-Gly-Gly-phospholipase C conjugates to trigger doxorubicin (Doxil ) release from cholesterol-stabilised distearoylphosphatidylcholine liposomes.…”
Section: Introductionmentioning
confidence: 99%
“…Although nonspecific multi-point conjugation of enzyme with polymer may result in a decrease in activity as previously reported [34,35], the VEMAC modification under optimized conditions is a simple and cost-effective strategy using a commercially available polymer that can be used to obtain fully active modified enzymes. Furthermore, VEMAC-Tryp contains many unmodified carboxyl groups that can be used for immobilization of VEMAC-Tryp on solid supports like particulate and porous materials, which is relevant to the design and development of bioreactors.…”
Section: Discussionmentioning
confidence: 83%
“…This approach links a succinic acid molecule to some hydroxyl groups of dextrin, thus obtaining a carboxyl group suitable for protein conjugation after activation, and it can thus be tuned for derivative control. Dextrin with a degree of succinylation and M W s in the ranges between 9%-32% mol and 7700-47,200 Da, respectively, were used to modify different proteins, such as phospholipase A2 [77], trypsin [78], melanocyte stimulating hormone [78] and epidermal growth factor (rhEGF) [79,80]. Dextrin conjugation proportionally reduced enzyme activity depending on the M W and the degree of succinylation.…”
Section: Dextrinmentioning
confidence: 99%
“…A new concept towards protein modification, called polymer-masking-unmasking-protein therapy (PUMPT), has been tested on dextrin [78]. The hypothesis was that polymer conjugation would protect a protein and mask its activity in transit while enabling controlled recovery of activity at the target site by triggered degradation of the polymeric component.…”
Section: Dextrinmentioning
confidence: 99%