Interviews with Faculty Researchers

– Interview with Prof. Wong Man-kin
Associate Dean, Faculty of Science & Professor, Department of Food Science and Nutrition

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.

In this context, Prof. Man Kin Wong's 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.

位點選擇性生物偶聯之進展 有助推進治療科學發展

– 黃文健教授專訪
理學院副院長及食品科學及營養學系教授

近年，針對離胺酸殘基和N-末端的多肽和蛋白修飾的生物偶聯方法成為了化學生物學的研究新方向。這些位點具有高反應性和可接近性，可以透過共價鍵把功能分子修飾於生物分子上，創造出具有多種用途的生物共軛物。

蛋白是生物的基本結構單元，在生物活動中發揮關鍵作用。在一些生物醫學應用中（如：藥物傳遞或靶向治療），由於蛋白不穩定的属性，需要加入額外功能分子才能發揮效用。傳統生物偶聯方法缺乏選擇性位點，導致這些生物製藥的質量下降和不穩定。因此，具有高準確性的位點選擇性生物偶聯方法有著越來越大的市場需求。

黃文健教授的研究團隊在這方面甚具心得。由於N-末端容易暴露於溶劑中，並且在修飾後對蛋白活性的干擾最小，因此他們致力研究針對N-末端的生物偶聯方法。團隊發現在微酸性條件下利用2-乙炔基苯甲醛（2-EBA）進行蛋白修飾，其選擇性會得到顯著改善，同時保留了蛋白的生物功能性。該方法在藥物傳遞和癌症治療等應用中都取得成果。

此外，黃教授的團隊還研發了新型可見光響應和熱響應生物偶聯試劑，為刺激響應型藥物傳遞、抗體藥物共軛物和細胞表面工程等帶來了新發展。透過利用光或溫度進行刺激反應，更能掌握生物共軛物的藥物釋放和標靶的準確度，旨在提高療效的同時減少藥物的副作用。

位點選擇性生物偶聯技術的發展是醫學研究的一大進展。黃教授的團隊旨在提高多功能治療生物共軛物的穩定性和療效，從而在藥物動力學上取得突破，更有效地治療人類疾病。他們的研究成果已發表了多篇學術論文，並申請了多項專利，亦與理大不同學系合作，以探索更多醫學應用的可能性。這種跨學科合作推動了化學生物學研究，期望為創新療法帶來了更好的臨床數據。