This technology enables precise, water-based chemical modification of proteins at their C-terminus using a single, easily removable reagent, preserving protein structure and function and allowing attachment of diverse functional groups for therapeutic, research, and diagnostic applications.
Background: Proteins and polypeptides play a central role in therapeutics, diagnostics, and biotechnology, driving the need for precise chemical modification techniques that preserve their native structure and function. Site-specific modification, particularly at the C-terminus, is highly desirable for creating homogeneous bioconjugates, improving drug efficacy, and enabling advanced protein engineering. However, the complexity of protein structures and their sensitivity to environmental conditions present significant challenges. The field has long sought methods that allow for efficient, selective, and biocompatible modifications in aqueous environments, as these conditions best maintain protein integrity and are compatible with physiological applications. Current approaches to protein modification often require pre-functionalization steps, such as the introduction of specific reactive groups, which can be labor-intensive and may compromise the protein’s native folding or biological activity. Many established protocols utilize harsh organic solvents or elevated temperatures, increasing the risk of protein denaturation and limiting their applicability to sensitive biomolecules. Additionally, existing methods frequently result in heterogeneous products due to poor site selectivity, complicating purification and reducing reproducibility—issues that are particularly problematic for therapeutic proteins where consistency and safety are paramount. The removal of by-products can also be cumbersome, further complicating downstream processing and increasing the risk of contamination. These limitations underscore the need for a more straightforward, selective, and gentle approach to C-terminal protein modification.
Technology Overview: This technology enables the selective chemical modification of protein and polypeptide backbones specifically at the C-terminus using a single, water-soluble reagent. Designed to function efficiently in aqueous environments, the method allows direct editing of the C-terminal amide bond without requiring any pre-functionalization or alteration of the protein’s native structure and function. The process supports the attachment of a wide variety of functional groups—including small molecules, peptides, proteins, and carbohydrates—resulting in stable, canonical amide bonds. The reagent and any by-products are easily removed post-reaction, simplifying purification and ensuring a clean, biocompatible end product. This approach has been successfully applied to therapeutically relevant proteins such as insulin and semaglutide, demonstrating its versatility and practical utility in drug development, protein engineering, and diagnostics. What differentiates this technology is its unique combination of selectivity, simplicity, and compatibility with physiological conditions. Unlike traditional protein modification methods that often require harsh chemicals, organic solvents, or pre-functionalization steps that can disrupt protein folding and function, this solution operates entirely in water under mild conditions, preserving the protein’s biological integrity. Its high specificity for the C-terminal amide bond ensures consistent, site-specific modifications, which is critical for reproducibility and safety in therapeutic applications. The ability to easily remove by-products and the flexibility to attach diverse functional groups further streamline downstream processing and broaden the range of possible applications. These features collectively position the technology as a significant advancement over existing protein modification strategies, offering a robust, efficient, and broadly applicable platform for next-generation biopharmaceutical and research applications.
https://suny.technologypublisher.com/files/sites/adobestock_1592615575.jpeg
Advantages: • Enables selective and site-specific chemical modification of protein C-terminus without pre-functionalization • Preserves native protein structure and biological function, ensuring therapeutic efficacy • Operates under mild, fully aqueous conditions compatible with sensitive proteins • Allows attachment of diverse functional groups, enabling customized bioconjugates • Produces stable, canonical amide bonds that maintain biocompatibility • Facilitates easy removal of reagent and by-products, simplifying purification • Broad applicability for therapeutic protein modification, drug development, and diagnostics
Applications: • Therapeutic protein drug modification • Homogeneous bioconjugate drug development • Site-specific antibody-drug conjugates • Protein-based diagnostic reagent engineering
Intellectual Property Summary: Select from the following Patent application filed
Stage of Development: • TRL 4 • https://en.wikipedia.org/wiki/Technology_readiness_level
Licensing Status: This technology is available for licensing.