Project Details
Projekt
Semisynthesis of natural glycoforms of human erythropoietin
Applicant
Professor Dr. Carlo Unverzagt
Subject Area
Biological and Biomimetic Chemistry
Term
from 2012 to 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 223435149
Due to its medical importance erythropoietin (EPO) is one of the best-studied recombinant therapeutic glycoproteins. In seminal studies it was revealed that the function of erythropoietin is highly dependent on the presence and the structure of its carbohydrate moieties. Despite many efforts the isolation of homogeneous EPO glycoforms is still not feasible and biological studies can only use mixtures of glycoforms. Thus, synthetic alternatives are desirable aiming at the generation of pure EPO glycoforms needed for detailed structure-activity-relationships. We have established a semisynthetic route to bioactive EPO with an Asn 24 N-glycan using a newly developed convergent synthesis for glycopeptides with all natural linkages. The glycan of Asn 24 can thus be varied readily in order to correlate systematically varied carbohydrate structures to the bioactivity of the protein, its intrinsic stability and the propensity to crystallize. A synthetic access to glycoforms of fully N- and O-glycosylated EPO will also be investigated. The systematic library of variants of natural glycoforms of EPO should provide general insights into the roles of carbohydrates in glycoproteins and may guide the future engineering of glycoforms.
DFG Programme
Priority Programmes
