Creative Biolabs offers the exclusive Hi-Affi™ phage display platform for custom CH2 domain antibody-like scaffold library construction. Through this proprietary technology, libraries with 100% precise mutant and over 1010 diversity can be generated.
CH2 domain (CH2D), also known as nanoantibody (nAb), the immunoglobulin (Ig) constant CH2 domain, is critical for the Ig effector functions. The structure of the constant antibody domains is similar to that of the variable domains consisting of β-strands connected mostly with loops or short helices. CH2, is unique in that it exhibits very weak carbohydrate-mediated interchain protein-protein interactions. Isolated CH2 is stable monomer in contrast to all other constant domains and most of the variable domains. It is the smallest (~12 kDa) independently folded antibody-like scaffold which is amenable to loop and β-sheet modifications that can be used to generate large libraries containing diverse binders to various antigens, and also confer some effector functions.
CH2D, as scaffold, has distinct advantages over large molecules and even other smaller antibody-like scaffolds. A fundamental limitation of large molecules is their poor penetration into tissues and absence to binding certain small regions which are accessible by smaller size molecules. While the existing smaller antibody-like scaffolds (less than 50kDa in size) is also restricted to their short circulating half-life due to rapid renal clearance. However, the CH2D has a longer serum half-life (8-16 hrs.) compared to other scaffolds of a similar molecular size. It can be better suited to linker and drug half-life for generating antibody-drug conjugates (ADCs), and the small size should deliver the cytotoxic drug to the tumor with improved efficacy and reduced toxicity. Therefore, CH2D may be of great interest and advantageous for pharmaceutical applications including cancer targeting and imaging.
Creative Biolabs has developed the proprietary Hi-Affi™ phage display platform to generate high quality scaffold protein libraries. This platform is built up from phage display technology, which is an exogenous gene expression method through fusing the target genes to bacteriophage coat proteins then displaying on the phage surfaces to select specific binders. Besides that, the trimer codon technology and NNK method have also been involved in this platform, which enable the controllable mutagenesis for library construction. Based on this platform, we can actually generate CH2D libraries with 100% precise mutant and the expected size of over 1010.
Creative Biolabs has successfully generated more than 50 custom scaffold libraries over the past decade. Our experienced scientists are confident in generating libraries to meet customers’ specific demand in the most satisfactory manner.
Fig. 1 Structure of the CH2 antibody domain and structural comparison with the corresponding region in the Fc and IgG structures. (Dimitrov 2009)