Development of Novel Recombinant Agonists and Antago-nists of Glycoprotein Hormones Using Site-Directed Mu-tagenesis and Gene Transfer

FUAD, FARES (2015) Development of Novel Recombinant Agonists and Antago-nists of Glycoprotein Hormones Using Site-Directed Mu-tagenesis and Gene Transfer. In: Third International Conference on Advances in Bio-Informatics, Bio-Technology and Environmental Engineering- ABBE 2015, 26 - 27 May,2015, Birmingham B42 2SU, UNITED KINGDOM.

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Abstract

One major issue regarding the clinical use of many peptides is their short half-life due to the rapid clearance from the circulation. To overcome this problem, we succeeded to ligate 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  (hCG) subunit. The CTP contains 28 amino acids with four O-linked oligosac-charide recognition sites. It was postulated that O-linked oligo-saccharides 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), thyrotropin (TSH), erythropoietin (EPO) growth hormone (GH) and thus to increase the longevity and bioactivity of these proteins in-vivo. Interestingly, the new analogs of FSH and GH were found not immunogenic in human and it is already passed successfully clinical trials phase III and phase II respectively. Moreover, FSH long acting was approved by the European Commission (EC) for treatment of fertility. In addition, our results indicated that long acting GH is not toxic in monkeys and the results from clinical trials phase I and phase II seem to be promising. Designing long acting peptides will diminish the cost of these drugs and perhaps reduce the number of injections in the clini-cal protocols.

Item Type: Conference or Workshop Item (Paper)
Uncontrolled Keywords: recombinant proteins, half-life, CTP, EPO, FSH, GH, TSH
Depositing User: Mr. John Steve
Date Deposited: 30 Apr 2019 11:41
Last Modified: 30 Apr 2019 11:41
URI: http://publications.theired.org/id/eprint/1732

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