Advancing in site-selective bioconjugation for enhanced therapeutic development
Bioconjugation, particularly targeting lysine residues and N-termini of peptides and proteins, has opened new avenues in chemical biology research. These sites, due to their reactivity and accessibility, are prime targets for attaching functional molecules. This process forms covalent bonds between biomolecules and other molecules, emerging as a potent tool for creating multifunctional bioconjugates with diverse applications.
Proteins, fundamental to organisms, fulfill critical roles in various biological activities. Yet, their instability and the need for additional functionalities for specific applications like drug delivery or targeting have led researchers to explore modification techniques. Traditional methods often lack selectivity, causing batch-to-batch inconsistencies and decreased efficacy. Hence, there's a growing demand for site-selective bioconjugation approaches enabling precise modification without compromising protein function.
Prof. Man Kin WONG, Associate Dean of the Faculty of Science and Professor of the Department of Food Science and Nutrition at The Hong Kong Polytechnic University, along with his research team, leads the forefront, focusing on the N-terminal modification of peptides and proteins. They have strategically targeted the N-terminus due to its solvent exposure and minimal interference with protein activities. By utilizing 2-ethynylbenzaldehydes (2-EBA) under slightly acidic conditions, they have achieved remarkable selectivity, enabling the modification of proteins while preserving their biological functions. This approach has shown promising results in various applications, including drug delivery systems and cancer therapeutics.
Moreover, Prof. Wong's team has expanded the scope of bioconjugation by developing novel visible light-responsive and thermal-responsive bioconjugation reagents. These advancements pave the way for stimuli-responsive drug delivery systems, antibody-drug conjugates and cell surface engineering. By harnessing the power of light or temperature stimuli, these bioconjugates provide improved control over drug release and targeting, enhancing therapeutic efficacy while minimizing side effects.
The development of site-selective bioconjugation technologies represents a significant advance in therapeutic research. Prof. Wong's team aims to improve the stability, efficacy and pharmaceutical kinetics of multifunctional therapeutic bioconjugates to treat human diseases more effectively. Their work has resulted in numerous academic papers and patents, with collaborations across departments at PolyU to explore wider medical applications. This interdisciplinary effort not only advances chemical biology research but also promises innovative therapeutics for potentially better clinical outcomes.
