UROP Proceedings 2022-23

School of Science Department of Chemistry 11 Design of Controllable Enzymes for Therapeutic Applications Supervisor: VONG, Kenward King Ho / CHEM Student: WAN, Kai Yui / SSCI Course: UROP1100, Fall The project focus on the synthesis and purification of the Mucin 1 N-terminus (MUC1-N) and Mucin 1 Cterminus (MUC1-C). It is believed that the two terminals can strongly interact with each other to form a complex, so they can provide us with a possible way to manipulate the conformation of other proteins containing one of the terminals and control their activity in vitro, serving therapeutic purposes. Further to the experiments carried out in the summer semester, new methods including tricine SDS-PAGE, FPLC in denatured condition, size exclusion, and dialysis are investigated to identify a better direction in producing the pure terminus effectively. Developing metal-catalyzed Reactions for Biological Applications Supervisor: VONG, Kenward King Ho / CHEM Student: CHENG, Ka Ki Ernest / CHEM Course: UROP1000, Summer This report presents the progress of the synthesis of unnatural amino acid (UAA) which is a planned model compound to investigate the feasibility of the proposed metal-catalyzed alkyne hydrothiolation peptide cleavage. Using homocysteine as the starting material, several modifications have been made to the synthetic scheme of UAA including change of protecting group, the addition of catalyst and reaction temperature and it will be described in the report. Until this point, the UAA is in the progress of synthesis, and that the deprotection and incorporation of inactivated alkyne to the UAA is required for further transformation of the UAA into peptide for subsequently exploration of the anticipated alkyne hydrothiolation of the peptide cleavage reaction to shed light on the localized release of cytotoxic onconase at the target tissues such as tumor tissues. The proposed mechanisms will also be described in order to provide the rationale behind this project. Developing metal-catalyzed Reactions for Biological Applications Supervisor: VONG, Kenward King Ho / CHEM Student: CHOY, Tsz Shan / CHEM Course: UROP1000, Summer In this study, gold-activated cell penetrating peptides are introduced for a different application. Using this strategy, relevant bioactive peptides are controlled by their charge to determine their level of penetration into the body. We present the development of activatable cell penetrating peptides (CPPs) by functionalizing them with an alkynylated biaryl-2-amine (ABA) group. In the presence of a gold catalyst, hydroamination and aromatization can produce positively charged phenanthridine for cellular uptake. In this study, 5 types of peptides, 2 types of substrates and 4 types of gold catalysts are used to test biological activity interchangeably in order to find the better match.