Bioorthogonal Metabolic Labeling Experiments to Introduce Undergraduate Students to Interdisciplinarity at the Interface of Chemistry and Biology

Chemists have always designed and deployed cross-disciplinaryapproachesthat interface chemistry with other disciplines to proffer solutionsto many human problems. We designed a laboratory experiment that implementschemistry concepts in a biological model to prime undergraduate studentsto appreciate interdisciplinarity as an approach to solving complexproblems in contemporary society. The experiments can also be implementedwith graduate students transitioning to chemical biology research.The experiment introduces students to classical and emerging chemistryand molecular biology techniques-mammalian cell culture, bioorthogonalmetabolic labeling, azide-alkyne cycloaddition reaction ("click"chemistry), microplate photometry, gel electrophoresis, and far-westernblot analysis-that are routinely used in research at the interfaceof chemistry and biology. The students cultured a Chinese hamsterovary cell line (CHO-K1) and metabolically labeled the cellular sialoglycanswith azide groups. Next, they used a click chemistry reaction to bioconjugatea fluorogenic molecule to the labeled sialoglycans, enabling the detectionof the glycans using microplate photometry or far-western blot analysis.The experiment created a context for a first-hand demonstration ofbioorthogonal chemical reaction, a concept novel to most undergraduateswith traditional chemistry (organic, inorganic, physical chemistry,and analytical) background. The experience allows the students toapply and connect organic chemistry, bioanalytical chemistry, andmolecular biology concepts while learning techniques such as microplatereading, SDS PAGE, and western blot imaging that are indispensableto the growing fields of drug discovery, chemical toxicology, chemicalbiology, and molecular biology. This experiment is ideal for preparingand motivating students to pursue future research opportunities atthe interface of chemistry and biology.