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Enhancing the Potency and Longevity of Highly Valuable Peptides Using Gene Fusion

Authors:
Fuad Fares
Naiel Azzam
Rinat Bar-Shalom
Avri Havron
Eyal Fima

Keywords: recombinant proteins; long acting; follitropin; thyrotropin; human chorionic gonadotropin; growth hormone; erythropoietin.

Abstract:
One major issue regarding the clinical use of many pep-tides is their short half-life in the body, due to the rapid clearance from the circulation. To overcome this issue, the carboxyl-terminal peptide of human chorionic gonadotropin  subunit was ligated to the coding sequence of follitropin, thyrotropin, erythropoietin and growth hormone. This peptide contains 28 amino acids and four O-linked oligosaccharide recognition sites. It was postulated that the O-linked oligosaccharides add flexibil-ity, hydrophilicity and stability to the protein. Ligation of this peptide to the coding sequence of these hormones has no effect on receptor binding and in vitro bioactivity. However it is dramatically increased half-life and bioactiv-ity in vivo. Interestingly, the new analogs of follitropin and growth hormone were found not immunogenic in human. Follitropin already passed successfully clinical trials phase III and approved by The European Commission for human use. In addition, our results indicated that long acting growth hormone is not toxic in monkeys and it passed suc-cessfully clinical trials phase II in adults. Other strategy to stabilize the peptide hormones was to convert the het-erodimeric structure to a single chain by fusing the subunits to a single gene with or without the carboxyl-terminal peptide of human chorionic gonadotropin  subunit. The single peptide chains of human thyroptropin were active and have longer half-life in the circulation.

Pages: 6 to 10

Copyright: Copyright (c) IARIA, 2012

Publication date: March 25, 2012

Published in: conference

ISSN: 2308-4383

ISBN: 978-1-61208-190-8

Location: St. Maarten, The Netherlands Antilles

Dates: from March 25, 2012 to March 30, 2012