DT in Nature:
Dityrosine (DT) bonds are observed throughout nature in structural proteins such as silk, elastin and collagen where the localized rigidity that DT bonds confer represents a selective advantage with respect to the structural proteins’ strength, toughness and elasticity. Examples of natural dityrosine crosslinks include human periodontal ligament collagen, aortic elastin, and keratin in skin and hair; structural proteins in plant cell walls; and the cuticles of insects and arthopods.
Dityrosine crosslinking is catalyzed in nature by a diverse group of metallo-enzymes, of which peroxidases are the most prevalent. Calder mimics the natural process of dityrosine crosslink formation, and we therefore use an enzyme that catalyzes the DT crosslinking reaction in nature, while otherwise preserving the structural integrity and functionality of substrate proteins. In so doing, we successfully harnessed this natural DT crosslinking process and now apply it in a targeted and highly controlled manner, to the design of conformationally-locked vaccine immunogens.
Dityrosine crosslinking is catalyzed in nature by a diverse group of metallo-enzymes, of which peroxidases are the most prevalent. Calder mimics the natural process of dityrosine crosslink formation, and we therefore use an enzyme that catalyzes the DT crosslinking reaction in nature, while otherwise preserving the structural integrity and functionality of substrate proteins. In so doing, we successfully harnessed this natural DT crosslinking process and now apply it in a targeted and highly controlled manner, to the design of conformationally-locked vaccine immunogens.