Poster Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

Immunomodulation of  N-glycolylneuraminic Acid  Glycans Using Nanotechnology Platform (#885)

Suraj Toraskar 1 , Preeti Chaudhary 1 , Raghavendra Kikkeri 1
  1. Indian Institute of Science Education and Research, PUNE, MAHARASHTRA, India

The sialic acid (Sia) family of sugars are terminally present on the cell surface with N-glycolylneuraminic acid (Neu5Gc) and N-acetylneuraminic acid (Neu5Ac) as the predominant form on most mammalian cells. Neu5Gc is deficient in humans due to an inactivating deletion in the CMAH gene encoding the hydroxylase responsible for the conversion of CMP-Neu5Ac to CMP-Neu5Gc. On the contrary, Neu5Gc is metabolically incorporated into human tissues from dietary sources (principally red meat), and also detected at even higher levels in human tumors. The up-regulation of sialylation in cancer might also explains, why ingested Neu5Gc preferentially accumulates in cancer tissues. Commensal bacteria incorporate dietary Neu5Gc into lipopolysaccharides, this leads to the generation of antibodies in human, ranging widely in levels among individuals. Currently known monoclonal antibody is unable to detect Neu5Gc in its native form and polyclonal antibody has less specificity and high background reactivity. Therefore generation of specific antibodies against Neu5Gc is essential which could be used as a potential marker for cancer. Herein we proposed the nanotechnology based platform to generate the specific antibodies against Neu5Gc glycans. We designed and synthesized 2,3 and 2,6 linked Neu5Gc trisaccharides, which were further conjugated to CRM protein and spherical gold nanoparticles of different sizes. These glycan functionalized nanoparticles and CRM protein was injected in mice and sera were collected at different time intervals. This serum was analyzed for antibody response using glycan microarray, which showed particularly IgG immune response against 2,3 linked Neu5Gc glycan.