BIOSYNTHESIS AND GLYCOSYLATION OF THYROTROPIN

点击翻译按钮获取中文摘要

Recombinant human thyrotropin has been produced after transient or stable transfection of alpha and hTSH-beta minigenes into various mammalian cell lines, including Chinese hamster ovary cells. Carbohydrate composition analysis shows that the recombinant TSH has more sialic acid than conventional pituitary TSH, which delays its metabolic clearance rate. Large scale production of recombinant TSH has been achieved by employing a hollow fiber bioreactor system as well as novel methods of purification. Various analogues of TSH have also been produced by modifying glycosylation or protein structure using site-directed mutagenesis. The specific role of carbohydrate in the action of TSH has been elucidated by use of differentially glycosylated subunits. Through a Cooperative Research and Development Agreement with the Genzyme Corporation (Boston), the Company and NIH are producing recombinant human TSH for clinical studies in patients with thyroid cancer. Approval of the Investigational New Drug Application and the commencement of clinical trials at NIH and four other medical centers is expected in late 1991.