Functionalized Semitelechelic Poly[N-(2-hydroxypropyl)methacrylamide] for Protein Modification

Citations Over TimeTop 17% of 1998 papers

Abstract

Semitelechelic poly[N-(2-hydroxypropyl)methacrylamide]s (ST-PHPMA) with different functional end groups, namely carboxyl, methyl ester, hydrazide, and amino groups, were prepared by chain transfer free-radical polymerization. 2,2'-Azobisisobutyronitrile (AIBN) was used as an initiator and 3-mercaptopropionic acid, methyl 3-mercaptopropionate, 3-mercaptopropionic hydrazide, and 2-mercaptoethylamine were used as chain-transfer agents. The semitelechelic polymers have been characterized by end-group analysis, size-exclusion chromatography (SEC), and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The effects of the concentrations of the mercaptans and the initiator on the molecular weight of the polymers have been investigated. The higher the concentration of mercaptan, the lower the molecular weight of ST-PHPMA. The concentration of initiator did not have a significant effect on the molecular weight of the semitelechelic polymers. The end groups of the ST polymers can be readily transformed by polymeranalogous reactions. A model protein, alpha-chymotrypsin, has been modified with ST-PHPMA-CONHNH2 and ST-PHPMA-COOSu and the conjugates characterized by MALDI-TOF MS. The activity of modified chymotrypsins toward a high molecular weight substrate, P-Gly-Leu-Phe-NAp (where P is the HPMA copolymer backbone, and NAp is p-nitroanilide), was slightly lower than the activity of the native enzyme. The cleavage of a low molecular weight substrate, Z-Gly-Leu-Phe-NAp, by modified chymotrypsins was dependent on their structure. Whereas the activity of the amino group modified chymotrypsins was higher than that of the native enzyme, the activity of carboxyl-modified chymotrypsins was lower than that of the native enzyme. In summary, the data seem to indicate that ST-PHPMA is an effective protein-modifying agent.

Related Papers

• → Reversible Addition–Fragmentation Chain Transfer Synthesis of a Micelle-Forming, Structure Reversible Thermosensitive Diblock Copolymer Based on the N-(2-Hydroxy propyl) Methacrylamide Backbone(2013)44 cited
• → RAFT Copolymerization with Crosslinking of Methyl Methacrylate and Ethylene Glycol Dimethacrylate in Supercritical Carbon Dioxide(2013)17 cited
• → Mathematical modeling of styrene and butyl acrylate homopolymerization via the reversible addition-fragmentation mechanism(2014)4 cited
• → Reversible Addition Fragmentation Chain Transfer Polymerization of Isobutyl Methacrylate(2004)7 cited
• The Influence of Different Initiators upon the Mechanism of Radical Reaction in the Synthesis of Polystyrenylphosphonous Acid(2002)