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Rational Design of Hyper-glycosylated Human Chorionic Gonadotropin Analogs (A Bioinformatics Approach)

[ Vol. 17 , Issue. 8 ]

Author(s):

Zahra Nabizadeh, Zarrin Minuchehr* and Ali Akbar Shabani*   Pages 1001 - 1014 ( 14 )

Abstract:


Background: Protein pharmaceuticals routinely display a series of intrinsic physicochemical instabilities during their production and administration that can unfavorably affect their therapeutic effectiveness. Glycoengineering is one of the most desirable techniques to improve the attributes of therapeutic proteins. One aspect of glycoengineering is the rational manipulation of the peptide backbone to introduce new N-glycosylation consensus sequences (Asn-X-Ser/Thr, where X is any amino acid except proline).

Methods: In this work, the amino acid sequence of human chorionic gonadotropin (hCG) was analyzed to identify suitable positions in order to create new N-glycosylation sites. This survey led to the detection of 46 potential N-glycosylation sites. The N-glycosylation probability of all the potential positions was measured with the NetNGlyc 1.0 server. After theoretical reviews and the removal of unsuitable positions, the five acceptable ones were selected for more analyses. Then, threedimensional (3D) structures of the selected analogs were generated and evaluated by SPDBV software. The molecular stability and flexibility profile of five designed analogs were examined using Molecular Dynamics (MD) simulations.

Results: Finally, three analogs with one additional N-glycosylation site (V68T, V79N and R67N) were proposed as the qualified analogs that could be glycosylated at the new sites.

Conclusion: According to the results of this study, further experimental investigations could be guided on the three analogs. Therefore, our computational strategy can be a valuable method due to the reduction in the number of the expensive, tiresome and time-consuming experimental studies of hCG analogs.

Keywords:

Rational design, hCG analogs, glycoengineering, hyper-glycosylated hCG, bioinformatic approach, hyperglycosylation.

Affiliation:

Dept. and Center for Biotechnology Research, Semnan University of Medical Sciences, Semnan, Department of Systems Biotechnology, Institute of Industrial and Environmental Biotechnology (IIEB), National Institute for Genetic Engineering and Biotechnology (NIGEB), P.O. Box 14965/161, Tehran, Dept. and Center for Biotechnology Research, Semnan University of Medical Sciences, Semnan

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