Research Project for Glycoprotein Engineering funded by Otsuka Chemical Co., Ltd.
Figure: Various biological phenomena mediated
by the glycans on cell surface
Glycan is an essential biomolecule for protein secretion and biological activity and is formed from the linking of sugar residues; more than 50% of human proteins are modified with glycan.
Our collaborator, Professor Yasuhiro Kajihara at Osaka University, has succeeded in developing a long-awaited technology for the large-scale preparation of intact human complex-type asparagine-linked glycans.
Kajihara and his colleagues also developed an efficient synthetic method for site-specific glycosylation of peptides using glycans, and they led the way to the complete chemical synthesis of glycoproteins. Otsuka Chemical Co., Ltd. has established commercial glycan production technology and has developed the related chemical synthesis of glycopeptides and glycoproteins.
We are focused on creating breakthrough pharmaceuticals based on those glycotechnologies in collaboration with Prof. Kajihara and Otsuka Chemical Co., Ltd. Our mission is to create innovative biopharmaceuticals of higher safety and value than any available therapeutic proteins.
Synthesis of human-type glycan and peptide glycosylation technology
Our collaborator, Professor Kajihara at the graduate school of science, Osaka University, and his colleagues have succeeded in developing a long-awaited technology for the large-scale chemo-enzymatic preparation of intact human complex-type asparagine-linked glycans. They also developed the efficient chemical synthetic methods for site-specific glycosylation of peptides.
Glycotechnology laboratory of Otsuka Chemical Co. Ltd. has been constructing the human-type glycan library and translating these technologies into the practical applications for the development of biopharmaceuticals.
Figure:
The
basic structure of the glycan used for the human-type
glycan library.
Figure: The pilot plant for synthesizing
human-type
glycan
Regulation of physical property and biological activity of peptides by glycosylation
To improve their physical properties and in vivo stability, we have developed a peptide glycosylation strategy using a chemoenzymatically synthesized human complex-type glycan.
To date, we have revealed that our technology represents an effective new peptide modification tool to improve the function of the same bioactive peptides as in existing peptide modification technologies.
Figure: Peptide glycosylation with the complex-type glycan to improve physical properties and in vivo stability.
Yamamoto, N. et al. Tetrahedoron Letters. 45,3287-3290, 2004.
Development of the technologies for chemical synthesis of glycoproteins
with the synthetic complex-type glycan
Kiriko Hirano et al., Angewandte Chemie International Edition 48, 9557–9560, 2009.
Prof. Kajihara and his colleagues have been developing an efficient chemical synthetic method for site-specific glycosylation of peptides using complex N-glycans and have pioneered the complete chemical synthesis of glycoproteins carrying one particular glycan structure.
We demonstrated that a chemically synthesized erythropoietin analog that carries 2 homogeneous human-type complex glycans and has similar biological activity as the recombinant erythropoietin in vitro.
We are promoting the establishment of a new manufacturing system of a therapeutically effective protein by comparing biological activity between synthetic glycoproteins and recombinant glycoproteins.
