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In silico design and analysis of a new hyperglycosylated analog of erythropoietin to improve drug efficacy

BACKGROUND: The enhancement of glycosylation by applying glycoengineering approaches has become widely used to boost properties for protein therapeutics. The objective of this work was to engineer a new hyperglycosylated analog of erythropoietin (EPO) with appropriately targeted N-linked carbohydrat...

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Autores principales: Kianmehr, Anvarsadat, Mohammadi, Hamid Shahbaz, Shokrgozar, Mohammad Ali, Omidinia, Eskandar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549927/
https://www.ncbi.nlm.nih.gov/pubmed/26322290
http://dx.doi.org/10.4103/2277-9175.161548
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author Kianmehr, Anvarsadat
Mohammadi, Hamid Shahbaz
Shokrgozar, Mohammad Ali
Omidinia, Eskandar
author_facet Kianmehr, Anvarsadat
Mohammadi, Hamid Shahbaz
Shokrgozar, Mohammad Ali
Omidinia, Eskandar
author_sort Kianmehr, Anvarsadat
collection PubMed
description BACKGROUND: The enhancement of glycosylation by applying glycoengineering approaches has become widely used to boost properties for protein therapeutics. The objective of this work was to engineer a new hyperglycosylated analog of erythropoietin (EPO) with appropriately targeted N-linked carbohydrates through bioinformatics tools. MATERIALS AND METHODS: The EPO protein sequence was retrieved from NCBI protein sequence database. Prediction of N-glycosylation sites for the target protein was done using the prediction server, NetNGlyc. The three-dimensional model of glycoengineered EPO (named as kypoetin) was constructed using the homology modeling program. Ramchandran plot obtained from PROCHECK server was used to check stereochemical property. Meanwhile, 3D model of kypoetin with attached N-carbohydrates was built up using the GlyProt server. RESULTS: In the new modified analog, three additional N-glycosylation sites at amino-acid positions 30, 34 and 86 were inserted. Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 3D structural modeling showed that attached carbohydrates were on the proper spatial position. The whole solvent accessible surface areas of kypoetin (15132.69) were higher than EPO (9938.62). CONCLUSIONS: Totally, various model evaluation methods indicated that the glycoengineered version of EPO had considerably good geometry and acceptable profiles for clinical studies and could be considered as the effective drug.
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spelling pubmed-45499272015-08-28 In silico design and analysis of a new hyperglycosylated analog of erythropoietin to improve drug efficacy Kianmehr, Anvarsadat Mohammadi, Hamid Shahbaz Shokrgozar, Mohammad Ali Omidinia, Eskandar Adv Biomed Res Original Article BACKGROUND: The enhancement of glycosylation by applying glycoengineering approaches has become widely used to boost properties for protein therapeutics. The objective of this work was to engineer a new hyperglycosylated analog of erythropoietin (EPO) with appropriately targeted N-linked carbohydrates through bioinformatics tools. MATERIALS AND METHODS: The EPO protein sequence was retrieved from NCBI protein sequence database. Prediction of N-glycosylation sites for the target protein was done using the prediction server, NetNGlyc. The three-dimensional model of glycoengineered EPO (named as kypoetin) was constructed using the homology modeling program. Ramchandran plot obtained from PROCHECK server was used to check stereochemical property. Meanwhile, 3D model of kypoetin with attached N-carbohydrates was built up using the GlyProt server. RESULTS: In the new modified analog, three additional N-glycosylation sites at amino-acid positions 30, 34 and 86 were inserted. Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 3D structural modeling showed that attached carbohydrates were on the proper spatial position. The whole solvent accessible surface areas of kypoetin (15132.69) were higher than EPO (9938.62). CONCLUSIONS: Totally, various model evaluation methods indicated that the glycoengineered version of EPO had considerably good geometry and acceptable profiles for clinical studies and could be considered as the effective drug. Medknow Publications & Media Pvt Ltd 2015-07-27 /pmc/articles/PMC4549927/ /pubmed/26322290 http://dx.doi.org/10.4103/2277-9175.161548 Text en Copyright: © 2015 Kianmehr. http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Original Article
Kianmehr, Anvarsadat
Mohammadi, Hamid Shahbaz
Shokrgozar, Mohammad Ali
Omidinia, Eskandar
In silico design and analysis of a new hyperglycosylated analog of erythropoietin to improve drug efficacy
title In silico design and analysis of a new hyperglycosylated analog of erythropoietin to improve drug efficacy
title_full In silico design and analysis of a new hyperglycosylated analog of erythropoietin to improve drug efficacy
title_fullStr In silico design and analysis of a new hyperglycosylated analog of erythropoietin to improve drug efficacy
title_full_unstemmed In silico design and analysis of a new hyperglycosylated analog of erythropoietin to improve drug efficacy
title_short In silico design and analysis of a new hyperglycosylated analog of erythropoietin to improve drug efficacy
title_sort in silico design and analysis of a new hyperglycosylated analog of erythropoietin to improve drug efficacy
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549927/
https://www.ncbi.nlm.nih.gov/pubmed/26322290
http://dx.doi.org/10.4103/2277-9175.161548
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