Earticle

초록

영어

Human alpha-1-antitrypsin (α1AT) is a glycoprotein with protease inhibitor activity protecting tissues from degradation. Patients with inherited α1AT deficiency are treated with native α1AT (nAT) purified from human plasma. In the present study, recombinant α1AT (rAT) was produced in Chinese hamster ovary (CHO) cells and their glycosylation patterns, inhibitory activity and in vivo half-life were compared with those of nAT. A peptide mapping analysis employing a deglycosylation reaction confirmed full occupancy of all three glycosylation sites and the equivalency of rAT and nAT in terms of the protein level. N-glycan profiles revealed that rAT contained 10 glycan structures ranging from bi-antennary to tetra-antennary complex-type glycans while nAT displayed six peaks comprising majorly bi-antennary glycans and a small portion of tri-antennary glycans. In addition, most of the rAT glycans were shown to have only core α(1,6)-fucose without terminal fucosylation, whereas only minor portions of the nAT glycans contained core and Lewis X-type fucose. As expected, all sialylated glycans of rAT were found to have α(2,3)-linked sialic acids, which was in sharp contrast to those of nAT, which had mostly α(2,6)-linked sialic acids. However, the degree of sialylation of rAT was comparable to that of nAT, which was also supported by an isoelectric focusing gel analysis. Despite the differences in the glycosylation patterns, both α1ATs showed nearly equivalent inhibitory activity in enzyme assays and serum half-lives in a pharmacokinetic experiment. These results suggest that rAT produced in CHO cells would be a good alternative to nAT derived from human plasma.

저자

• Kyung Jin Lee [ Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon, Korea, Department of Biological Science, Wonkwang University, Iksan, Korea ]
• Sang Mee Lee [ Alteogen Inc., Bioventure town, Daejeon, Korea.3Department of Biotechnology, Hannam University, Daejeon, Korea. ]
• Jin Young Gil [ Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon, Korea. Department of Biotechnology, Hannam University, Daejeon, Korea. ]
• Ohsuk Kwon [ Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon, Korea. ]
• Jin Young Kim [ Korea Basic Science Institute, Chungbuk, Korea, 5Department of Biological Science, Wonkwang University, Iksan, Korea ]
• Soonjae Park [ Alteogen Inc., Bioventure town, Daejeon, Korea ]
• Hye-Shin Chung [ Alteogen Inc., Bioventure town, Daejeon, Korea. Department of Biotechnology, Hannam University, Daejeon, Korea. ]
• Doo-Byoung Oh [ Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon, Korea. ]

참고문헌

발행기관

간행물

표지보기 관심저널 등록

• 간행물명

  한국당과학회 학술대회

• 간기

  연간

• 수록기간

  2006~2022

• 십진분류

  KDC 517 DDC 614