A Strategy for Tumor Targeting by Higher-Order Glycan Pattern Recognition: Synthesis and In Vitro and In Vivo Properties of Glycoalbumins Conjugated with Four Different N-Glycan Molecules

Small. 2020 Nov;16(46):e2004831. doi: 10.1002/smll.202004831. Epub 2020 Oct 20.


Natural glycoconjugates that form glycocalyx play important roles in various biological processes based on cell surface recognition through pattern recognition mechanisms. This work represents a new synthesis-based screening strategy to efficiently target the cancer cells by higher-order glycan pattern recognition in both cells and intact animals (mice). The use of the very fast, selective, and effective RIKEN click reaction (6π-azaelectrocyclization of unsaturated imines) allows to synthesize and screen various structurally well-defined glycoalbumins containing two and eventually four different N-glycan structures in a very short time. The importance of glycan pattern recognition is exemplified in both cell- and mouse-based experiments. The use of pattern recognition mechanisms for cell targeting represents a novel and promising strategy for the development of diagnostic, prophylactic, and therapeutic agents for various diseases including cancers.

Keywords: N-glycoalbumins; biodistribution; higher-order heterogeneity; pattern recognition; tumor targeting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Glycation End Products, Advanced
  • Glycoconjugates
  • Mice
  • Neoplasms*
  • Polysaccharides*
  • Serum Albumin


  • Glycation End Products, Advanced
  • Glycoconjugates
  • Polysaccharides
  • Serum Albumin
  • glycated serum albumin