James P. Tam
Nanyang Technological University, Singapore
Finding from Nature a New Paradigm for Orally-Active and Cell-penetrating Bioactive Microproteins
Murray Goodman Scientific Excellence & Mentorship Award
Monday, June 26, 2023, at 05:25 pm - 05:55 pm
A continuing challenge in discovery of peptide therapeutics from natural products is to find a new paradigm that target intracellular protein-protein interactions. An under-explored group of natural products that could fit such a paradigm is the family of super cystine-dense peptides or microproteins with 6-10 cysteine and 2-4 kDa in MW. They have sufficiently large footprints for on-target specificity and highly compact structures to resist proteolytic degradation.
Although cysteine-rich peptides of 2-7 kDa are found in hormones, growth factors, antimicrobials and toxins, few are orally active or cell- penetrating. Guided by traditional medicines, our laboratory has a long-standing research program in the discovery of orally-active super cystine-dense microproteins from medicinal plants.
Here, I will present our 25-year venture into their discovery, target identification, chemical synthesis of bioactive super cystine-dense microproteins. I will also present a new method for their chemical synthesis through an ultrafast oxidative folding that completes within a second. Our discoveries of "first-in-class" bioactive microproteins could provide therapeutic leads to address several prevalent health issues: cardiovascular diseases, stress and frailty, the underlying causes of numerous chronic and old-age-related diseases.
This research was supported in part by a Competitive Research Grant by the Nanyang Technological University Internal Funding - Synzyme and Natural Products, SYNC.
Professor James P. Tam is the Professor of the Herbalomics and Drug Discovery Laboratory and Lee Wee Nam Professor of School of Biological Sciences, Nanyang Technological University, Singapore since 2001. Since 2008, he is also the Director of Synzymes and Natural Products Center (SYNC).
Tam received his Ph.D. in Medicinal Chemistry from the University of Wisconsin, Madison, USA in 1976 and held appointments as Associate Professor at The Rockefeller University, USA (1982-1992), Professor at Vanderbilt University, USA (1992-2004) and The Scripps Research Institute, USA (2004-2008). Tam later moved on to Nanyang Technological University, Singapore where he held active appointments as Founding Dean and the Founding Director of Biological Research Center of the School of Biological Sciences (2001-2007). He also served as the Founding Director of the double-degree program in Biomedical Sciences and Chinese Medicine (2008-2012).
Tam’s research work focuses on the discovery, design and development of therapeutics, particularly orally active biologics, immunologics and anti-infectives. He is also actively involved in peptide and protein chemistry, selective chemoenzymatic ligation for peptides, proteins and dendrimers, synthesis and oxidative folding of cysteine-rich peptides where he has published more than 330 papers in these areas of research.