Antibody Complementary Determining Region of Heavy-Chain 3 (CDR-H3) Mimics Used as a Peptide Scaffolding Platform for Drug Discovery

Abstract

Traditional monoclonal antibodies are widely used for targeting specific proteins in therapeutic applications, but they face significant limitations. Due to their large molecular size, antibodies often demonstrate poor tissue penetration, reducing their effectiveness in targeting tumors and other dense tissues. Additionally, their lack of oral bioavailability and risks of immunogenicity pose additional treatment challenges. As a result, there is a critical need for smaller and more stable molecules that can provide high-affinity binding without the limitations of full-sized antibodies.

Researchers at Florida Atlantic University have developed an innovative platform technology featuring ADAPTins—engineered β-hairpin peptides that closely mimic antibody CDR-H3 loops. This innovation addresses the limitations of traditional antibodies by offering a smaller, stable molecules with high binding affinity. Unlike full-sized antibodies, ADAPTins are designed to penetrate cell membranes and dense tissues effectively, potentially increasing therapeutic efficacy in tumors and reducing immune response risks. The technology inspired by the modularity and adaptability of CDR-H3s combines a β-strap and a β-bulge subunit to create a robust scaffold (MW 2-3 kDa; surface > 300Å2) capable of selective protein binding and modulation of protein-protein interactions (PPIs). Currently, this platform is in the preclinical development stage, with ongoing studies to validate its stability and effectiveness on various therapeutic targets.

FAU seeks to advance this innovation into the marketplace through licensing or development partnerships.

Benefit

Market Application

Publications

De Novo Synthesis and Structural Elucidation of CDR-H3 Loop Mimics