The GlyCanDrug research program envisions approaching the cancer glycome with two cohesive and complementary scientific objectives that have a common target: key cancer-associated glycans that tumors exploit to develop enabling cancer features.

These consist of:

  • Scientific Objective 1:
    a precise inhibition of the expression of cancer-associated glycans thus affecting their functional role in cancer progression;
  • Scientific Objective 2:
    the development of cutting-edge tools that target those key cancer-associated glycans that are uniquely expressed on cancer cells.

GlyCanDrug designed the following 10 cutting-edge individual projects:

  • DC1: Synthesis of fucose and sialic acid mimetics able to selectively disrupt the function of key glycosyltransferases implicated in cancer. (University of Florence, Florence, ITALY). Link
  • DC2: Synthetic approaches for targeting cancer glycosylation. (University of Florence, Florence, ITALY). Link
  • DC3: Evaluation of glycosyltransferases inhibitors and targeted approaches in cancer cells and tumour spheroids. (i3S-Instituto De Investigação E Inovação Em Saúde Da Universidade Do Porto, Porto, PORTUGAL). Link
  • DC4: Protein expression and purification of FTs and crystallization of FTs and STs complexed to inhibitors. (Universidad De Zaragoza, Zaragoza, SPAIN). Link
  • DC5: Combotope-specific single chain fragments (scFv) antibodies by Phage Display Technologies. (Danmarks Tekniske Universitet, Copenhagen, DENMARK). Link
  • DC6: Assay development and activity screening of inhibitors of sialyl and fucosyltransferases. (Danmarks Tekniske Universitet, Copenhagen, DENMARK). Link
  • DC7: Screening and hit development towards novel non-carbohydrate inhibitors of glycosyl transferase. (Univerza V Ljubljani, Ljubiana, SLOVENIA). Link
  • DC8: Structural and dynamics characterization of the complexes of bioactive molecules with GTs and scFv antibodies by NMR. (Agencia Estatal Consejo Superior De Investigaciones Cientificas, Siviglia, SPAIN). Link
  • DC9: Expression, purification and characterization of sialyltransferases, and validation of glycosyltransferases inhibitors using microplate assays. (Centre National de la Recherche Scientifique, Lille, FRANCE). Link
  • DC10: Testing and validation of inhibitors by engineered cell-based glycan arrays. Glycodisplay Aps, Copenhagen, DENMARK). Link

WP1

Design and synthesis of bioactive molecules that target aberrant glycosylation in cancer

WP1 aims to develop new fucosyltransferases (FTs) and sialyltransferases (STs) inhibitors that will be validated in biochemical assays. The activities of WP1 include also the identification of Golgi targeting molecules, the development of high-throughput methodologies for the fast screening of FTs/STs inhibitors. Moreover, specific single-chain variable fragment antibodies that targets Tn-/sTn antigens will be developed.

Lead beneficiary: UNIFI

WP2

Structural and functional characterization, and validation of GlyCanDrug bioactive molecules.

WP2 aims to validate the svFv antibodies and the FTs/STs inhibitors in human cacer cell models. The activities of WP2 include also the development of nanomaterials for the precision targeting of cancer cells.

Lead Beneficiary: DTU