At Last: Erythropoietin as a Single Glycoform

Wang, Ping; Dong, Suwei; Brailsford, John A.; Iyer, Karthik; Townsend, Steven D.; Zhang, Qiang; Hendrickson, Ronald C.; Shieh, Jae‐Hung; Moore, Malcolm A.S.; Danishefsky, Samuel J.

doi:10.1002/anie.201206090

Cited by 72 publications

(36 citation statements)

References 67 publications

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“…With the advent of large-scale cell culture for bioprocess applications (e.g., antibody production in the pharmaceutical industry), steady advances have increased the bioprocess protein yield 100-fold since the mid-1980s [152], [153]. Hence, it is not unreasonable to think that, while current projected costs for whole lung culture are very high, these costs may come down with increased efficiency of culture medium utilization and bioreactor improvements.…”

Section: Bioreactorsmentioning

confidence: 99%

Strategies for Whole Lung Tissue Engineering

Calle

Ghaedi

Sundaram

et al. 2014

IEEE Trans. Biomed. Eng.

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Recent work has demonstrated the feasibility of using decellularized lung extracellular matrix scaffolds to support the engineering of functional lung tissue in vitro. Rendered acellular through the use of detergents and other reagents, the scaffolds are mounted in organ-specific bioreactors where cells in the scaffold are provided with nutrients and appropriate mechanical stimuli such as ventilation and perfusion. Though initial studies are encouraging, a great deal remains to be done to advance the field and transition from rodent lungs to whole human tissue engineered lungs. To do so, a variety of hurdles must be overcome. In particular, a reliable source of human-sized scaffolds, as well as a method of terminal sterilization of scaffolds, must be identified. Continued research in lung cell and developmental biology will hopefully help identify the number and types of cells that will be required to regenerate functional lung tissue. Finally, bioreactor designs must be improved in order to provide more precise ventilation stimuli and vascular perfusion in order to avoid injury to or death of the cells cultivated within the scaffold. Ultimately, the success of efforts to engineer a functional lung in vitro will critically depend on the ability to create a fully endothelialized vascular network that provides sufficient barrier function and alveolar-capillary surface area to exchange gas at rates compatible with healthy lung function.

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Section: Bioreactorsmentioning

confidence: 99%

Strategies for Whole Lung Tissue Engineering

Calle

Ghaedi

Sundaram

et al. 2014

IEEE Trans. Biomed. Eng.

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“…In our first total synthesis of homogeneously glycosylated EPO, we chose to include three simpler chitobiose units and the naturally-abundant glycophorin tetrasaccharide at the four native glycosylation sites [98]. From a retrosynthetic perspective, we envisioned gaining access to the full-length glycoprotein, EPO[1–166], by assembling four glycopeptide domains through iterative NCL-based ligations (Scheme 12).…”

Section: Chemical Synthesis Of Glycoproteinsmentioning

confidence: 99%

Total Synthesis of Glycosylated Proteins

Fernández‐Tejada

Brailsford

Zhang

et al. 2014

Topics in Current Chemistry

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Glycoproteins are an important class of naturally occurring biomolecules which play a pivotal role in many biological processes. They are biosynthesized as complex mixtures of glycoforms through post-translational protein glycosylation. This fact, together with the challenges associated with producing them in homogeneous form, has hampered detailed structure-function studies of glycoproteins as well as their full exploitation as potential therapeutic agents. By contrast, chemical synthesis offers the unique opportunity to gain access to homogeneous glycoprotein samples for rigorous biological evaluation. Herein, we review recent methods for the assembly of complex glycopeptides and glycoproteins and present several examples from our laboratory towards the total chemical synthesis of clinically relevant glycosylated proteins that have enabled synthetic access to full-length homogeneous glycoproteins.

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“…Mittels der Anwendung von Verfahren der rekombinanten Synthese, der ortsspezifischen Aminosäure-mutation und der chemischen Synthese wurden eindrucksvolle Fortschritte erzielt, die zu verbesserten Kenntnissen von EPO sowie des breiteren Gebiets der Glycoproteinsynthese geführt haben. Dennoch kann es keinen Zweifel geben, dass vor unserem 2012 erschienen Bericht [16] keine Totalsynthese von EPO erreicht wurde. Nach unseren oben definierten Kriterien muss eine Totalsynthese von EPO das Glycoprotein mit der nativen Aminosäuresequenz und mit Kohlenhydratdomänen an allen nativen Glycosylierungsstellen erzeugen.…”

Section: Epo-forschung Richardson Und Macmillan Beschrieben Dieunclassified

Der gewundene Pfad zum Erythropoietin entlang der Grenze von Chemie und Biologie

2013

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Die Totalsynthese eines homogenen Erythropoietins (EPO), das die native Aminosäuresequenz aufweist und Chitobioseglycane an jeder der drei N‐glycosylierten Wildtyp‐Stellen trägt, wurde in unserem Laboratorium erzielt. Wir beschreiben in diesem Kurzaufsatz unsere ein Jahrzehnt dauernden Forschungsbemühungen um die Synthese dieser anspruchsvollen Zielverbindung. Entscheidend für den Erfolg war das Zusammenspiel zwischen Biologie und Chemie, den beiden Grundpfeilern der Naturwissenschaften.

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At Last: Erythropoietin as a Single Glycoform

Cited by 72 publications

References 67 publications

Strategies for Whole Lung Tissue Engineering

Strategies for Whole Lung Tissue Engineering

Total Synthesis of Glycosylated Proteins

Der gewundene Pfad zum Erythropoietin entlang der Grenze von Chemie und Biologie

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