Preparation and characterization of methoxy polyethleneglycol-modified urokinase = 메톡시 폴리에틸렌글라이콜에 의한 유로키나제의 변형

Urokinase (EC.3.4.21.31), a serine protease, has been used clinically for treatment of thrombosis and/or vascular obstructions. The in vivo half life of urokinase, however, is very short and hence large amounts of urokinase and repeated injections are required for enough fibrinolytic potential in vivo, which causes some side effects. To improve these disadvantages of urokinase, the modification of urokinase was performed by using methoxy-polyethyleneglycol activated with cyanuric chloride. The degrees of modification were determined by 2,4,6-trinitrobenzenesulfonate methods and the activity of urokinase was assayed by S-2444 chromogenic methods. The remaining activity of urokinase after modification was reduced as the degrees of modification increased and the in vitro stability of modified-urokinase after incubation in human serum was much larger than native urokinase``s. The heat-stability of urokinase could be increased by polyethyleneglycolmodification but pH-stability of urokinase was relatively independent on modification except for a slight resistance of modified-urokinase to extreme alkaline pH. The modification of urokinase with polyethyleneglycol caused a significant decrease of antigenicity presumably by masking of antigenic sites of modified urokinases. The in vivo stability of urokinase was investigated in rats and it was observed that the half life of modified urokinases was increased with modification degrees. From these results possible effects of polyethyleneglycol moieties of modified-uorkinase on both in vitro and in vivo stabilities of urokinase activity and the possibility of clinical usage of methoxy polyethyleneglycol-modified urokinases are discussed.
Advisors
Byun, Si-Myungresearcher변시명researcher
Publisher
한국과학기술원
Issue Date
1992
Identifier
60356/325007 / 000901203
Language
eng
Description

학위논문(석사) - 한국과학기술원 : 생물공학과, 1992.2, [ vi, 49 p. ]

URI
http://hdl.handle.net/10203/27740
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=60356&flag=t
Appears in Collection
BS-Theses_Master(석사논문)
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