Research Progress in Area 4 方向 ( 四 ) 課題進展 189 Abstract The enormous numbers ofmarine organisms from ocean offer great opportunities to screen for lead compounds possessing antibacterial, anticancer, neuroprotective, anti-fungal, anti-malarial, antiinflammatory, and anti-microbial properties with unimaginable structural diversities for new drug developments. In this proposal, prof. Zhu’s group aims to screen for anti-cancer, anti-HIV (human immunodeficiency virus) and anti-ALS/FTD (amyotrophic lateral sclerosis and frontotemporal dementia) lead compounds from marine natural products targeting human DNA replication nucleoprotein complexes and G-quadruplex DNAs with the use of NMR, to determine their complex structures by NMR and x-ray crystallography to characterize anti-bacterial peptide, to conduct mechanistic study of enzymes in biosynthetic pathways of lasso peptides by x-ray, NMR and cryo-EM, and finally to help other team members on study of metabolomics and compound optimization. Research Activities and Progress • Tested the binding between marine natural products and human cancer, HIV and ALS targets; • Determined F10 structures and will soon determine the F10/G-quadruplex structure. Key Findings • A marine bioactive compound F10 specifically binds to G4C2 G-quadruplex DNA (Fig.1); • His group determined the solution structure of F10 with the use of NMR and with the help from x-ray structural data (Fig.1).; • His group also found that F10 bound to human hnRNP protein and blocked the binding between hnRNP and G4C2 G-quadruplex; • A marine bioactive compound ALBO was found to bind HIV target (Fig.2). Research Output Publication 1 Trained personnel 3 Patent 2 Structure-functional Characterization of Bioactive Marine Natural Products and Metabolomics by NMR Prof. Guang Zhu The Hong Kong University of Science and Technology Fig 1. Structure model of F10/G4C2 complex. (Geng et al (2021), NAR; Xu et al (2020) NAR; Qian et al (2020) US patent No 63/078,697
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