Production und characterization of recombinant human lactoferrin

作者: Henricus Antonius , van Veen

DOI:

关键词:

摘要: Human lactoferrin (hLF) is an iron-binding glycoprotein of Mr 77,000 that belongs to the transferrin family. Based on extensive research showing antimicrobial, anti-inflammatory and immunomodulatory activities hLF, molecule postulated be involved in innate host defence against infection severe inflammation. The diverse biological properties hLF may allow for a variety applications human healthcare. However, limited availability (human milk-derived) natural has been major hurdle (clinical) studies potential applications. To overcome this limitation feasibility large-scale production functional recombinant (rhLF) was studied. This thesis reports use transgenic cows as protein technology rhLF describes characterization safety testing purified molecule. The bovine mammary gland appears attractive vehicle producing large amounts constant expression levels, gram per liter range, have obtained without affecting normal milk parameters. Characterization revealed closely matches structure except differences glycosylation. differential glycosylation pattern did not result difference between any employed vitro vivo assay systems. Furthermore, various preclinical toxicity Phase I clinical study safe well tolerated. Taken together, are valuable platform application

参考文章(42)
Tim Edmunds, Scott M. Van Patten, Julie Pollock, Eric Hanson, Richard Bernasconi, Elizabeth Higgins, Partha Manavalan, Carol Ziomek, Harry Meade, John M. McPherson, Edward S. Cole, Transgenically Produced Human Antithrombin: Structural and Functional Comparison to Human Plasma–Derived Antithrombin Blood. ,vol. 91, pp. 4561- 4571 ,(1998) , 10.1182/BLOOD.V91.12.4561
P. Zhang, V. Sawicki, A. Lewis, L. Hanson, J. H. Nuijens, M. C. Neville, Human Lactoferrin in the Milk of Transgenic Mice Increases Intestinal Growth in Ten-Day-Old Suckling Neonates Advances in Experimental Medicine and Biology. ,vol. 501, pp. 107- 113 ,(2001) , 10.1007/978-1-4615-1371-1_13
M Migliorini, E Romm, D M Mann, Delineation of the glycosaminoglycan-binding site in the human inflammatory response protein lactoferrin. Journal of Biological Chemistry. ,vol. 269, pp. 23661- 23667 ,(1994) , 10.1016/S0021-9258(17)31566-1
Ghislain Opdenakker, Pauline M. Rudd, Christopher P. Ponting, Raymond A. Dwek, Concepts and principles of glycobiology. The FASEB Journal. ,vol. 7, pp. 1330- 1337 ,(1993) , 10.1096/FASEBJ.7.14.8224606
Jan H. Nuijens, Patrick H. C. van Berkel, Floyd L. Schanbacher, Structure and biological actions of lactoferrin Journal of Mammary Gland Biology and Neoplasia. ,vol. 1, pp. 285- 295 ,(1996) , 10.1007/BF02018081