Donadio-Andrei S.,SiamedXpress |
Mai N.E.,SiamedXpress |
Nicollo M.,SiamedXpress |
Carbohydrate Chemistry | Year: 2014
Gonadotropins are a family of three glycoprotein hormones (FSH, LH and hCG) essential for steroid production and reproductive functions. Over the past two decades, these glycoproteins either from extractive origin or produced by recombinant technology have been marketed for assisted reproductive techniques. Recombinant gonadotropins are produced by rodent cell lines which display glycosylation machinery different from human cells and often add undesired carbohydrate determinants which may alter protein folding, induce immunogenicity and overall reduce circulatory half-life of the drug. Notably, they fail to transfer sialic acid as N-acetylneuraminic acid (Neu5Ac) in a α 2,6-linkage as in the natural endocrine cells and this affects their activity and duration in blood. We have designed ST6Gal minigenes to optimize sialic acid transfer in the most common drug-approved cell line i.e the Chinese Hamster Ovary cells. We present herein various strategies that may be used to produce a2,6-sialylated gonadotropins. A level of 60-90% of sialylation may be routinely achieved depending on the enzymeminigene used to equip the producer clone. © The Royal Society of Chemistry 2014.