Endocrine Abstracts

One major issue regarding the clinical use of many peptides is their short half-life span in the body, due to the rapid clearance from the circulation. Thus, at the clinical level, there is a need for a regime of frequent injections of the peptides into the patients to overcome this low stability factor. To overcome this problem, we succeeded to add the signal sequence of O-linked oligosaccharides to the coding sequence of the hormones. The cassette gene that has been used contains the sequence of the carboxyl-terminal peptide (CTP) of human chorionic gonadotropin-β (hCG-β) subunit. The CTP contains 28 amino acids and four O-linked oligosaccharide recognition sites. It was postulated that the O-linked oligosaccharides add flexibility, hydrophilicity and stability to the protein. On the other hand it was suggested that the four O-linked oligosaccharides play an important role in preventing plasma clearance and thus increasing the half-life of the protein in circulation. Using this strategy we succeeded to ligate the CTP to the coding sequence of follitropin (FSH), TSH, erythropoietin (EPO) GH, interferon β and thus to increase the longevity and bioactivity of these proteins in vivo. Interestingly, the new analog of FSH was found not immunogenic in humans and it is already passed successfully clinical trials phase III and approved by The European Commission (EC). In addition, our results indicated that long acting GH is not toxic in monkeys and it passed successfully clinical trials phases I and II and the protocol for phase III was approved. The preliminary results regarding interferon β seem to be promising. Thus, using this technology seems to be promising in designing long acting peptides. Development of long acting peptides will diminish the cost of these drugs and perhaps reduce the number of injections in clinical protocols.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.