Media.Player

Sited-Directed Pegylation of Arginases and the use thereof as Anti-Cancer and Anti-Viral Agents

Summary

Mono-pegylated arginase conjugate and method producing thereof. The mono-pegylated arginase is homogeneous in molecular weight and shows therapeutic effect for treating cancers and viral infections. The method of producing such arginase conjugate has a main step of genetically modifying the gene encoding an arginase so that the PEG moiety can attach to the enzyme at a predetermined, specific intended site. This is achieved by removing the PEG attaching amino acid residues at undesirable sites while keeping (or adding, if necessary) the one at the desirable site of the enzyme. Two exemplary mono-pegylated arginase conjugates so produced are human arginase I (HAI) where a polyethylene glycol (PEG) moiety is site-specific covalently bonded to Cys45 of the enzyme and Bacillus caldovelox arginase (BCA) where a polyethylene glycol (PEG) moiety is site-specific covalently bonded to Cys161 of the enzyme.

Supplementary Information

Inventor: Leung, Yun Chung | Lo, Wai-hung
Priority Number: US8507245B2
IPC Current: C12N000978 | C07K001400 | C12P002100
US Class: 435227 | 4350691 | 530350 | 930240 | 930320
Assignee Applicant: The Hong Kong Polytechnic University
Title: Site-directed pegylation of arginases and the use thereof as anti-cancer and anti-viral agents
Usefulness: Site-directed pegylation of arginases and the use thereof as anti-cancer and anti-viral agents
Summary: The conjugate is useful in treating an arginine-dependant disease, which is: cancer, which is either arginine deiminase (ADI)-sensitive or ADI-resistant with substantially no ornithine transcarbamylase (OTC) expression; or an infection by a virus comprising HIV, hepatitis C virus or hepatitis B virus (all claimed). The ability of the conjugate to treat HIV infection was tested in H9 cells (human lymphoblastoid cell line) inoculated with HIV strain RF. The result showed that the conjugate (Cys45 pegylated human arginase I) exhibited an IC 50 value of 37 U/ml.
Novelty: New polyethylene glycol (PEG)-arginase conjugate comprising a PEG moiety covalently attached to arginase (e.g. human arginase I) at a predetermined position, useful in treating an arginine-dependant disease (cancer or viral infection)

Industry

Disease Diagnostic/Treatment

Sub Category

HIV

Others

LEUNG Yun-Chung Thomas
LO Wai-Hung Thomas

Country/Region

USA