Structural Approaches for Targeted Therapy

Tumor associated carbohydrate antigens (TACAs) are a class of glycans with important structural and signaling functions playing a major role in cell proliferation, differentiation, and apoptosis relevant to oncology. Structure-based approaches have been used to study antigen-antibody interactions in the tumor micro-environment and a peptidyl ligand was also designed that mimics the molecular topology of TACAs even though they are chemically dissimilar but functionally equivalent molecular structures. This work on antibody-TACA interactions suggests that in designing antibodies, careful consideration should be made in using mutations that enhance the rigidity of an antibody. This work also suggests that electrostatics play a major role in the recognition of the model antigen examined. Discrimination against wanted targets through repulsive electrostatic interactions might be more fruitful than a strong optimization of target binding. Increased specificity toward one target leads to decreased affinity towad others.