Piperidine-based glycodendrons as protein N-glycan prosthetics.
The generation of homogeneously glycosylated proteins is essential for defining glycoform-specific activity and improving protein-based therapeutics. We present a novel glycodendron prosthetic which can be site-selectively appended to recombinant proteins to create 'N-glycosylated' glycoprotein mimics. Using computational modeling, we designed the dendrimer scaffold and protein attachment point to resemble the native N-glycan architecture. Three piperidine-melamine glycodendrimers were synthesized via a chemoenzymatic route and attached to human growth hormone and the Fcregion of human IgG. These products represent a new class of engineered biosimilars bearing novel glycodendrimer structures.
Department of Chemistry, University of California Berkeley, CA 94720, USA.
Jason E
JE
Hudak
Department of Chemistry, University of California Berkeley, CA 94720, USA.
Brian
B
Belardi
Department of Chemistry, University of California Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California Berkeley, CA 94720, USA.
Mason J
MJ
Appel
Department of Chemistry, University of California Berkeley, CA 94720, USA.
Angelo
A
Solania
Department of Chemistry, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
Peter V
PV
Robinson
Department of Chemistry, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA. Electronic address: bertozzi@stanford.edu.
Carolyn R
CR
Bertozzi
D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D010880:Piperidines / Q000737:chemistry*; D011134:Polysaccharides / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*; D014227:Triazines / Q000737:chemistry
D050091:Dendrimers; D010880:Piperidines; D011134:Polysaccharides; D011506:Proteins; D014227:Triazines; C032727:piperidine; C011907:melamine
Chemoenzymatic synthesis; Glycodendrimer; Glycoprotein; Oxime; Protein engineering