Speaker: Lisa Jenkins, National Cancer Institute
Topic: Investigation into the Mechanism and Targets of an Antiviral Zinc Finger Inhibitor
Date: Monday, May 11, 2026
Time: 6:15 pm Dinner, 7:15 pm Presentation
Location: Shimadzu Scientific Instrument, Inc. Training Center 7100 Riverwood Drive, Columbia, MD 21046 (Directions)
Dinner: Please RSVP to Sheng Feng (SFeng@som.umaryland.edu) by Friday, May 9 if you will be attending the dinner.
Abstract: Covalent modification of target proteins is a well-established mechanism of action for small molecule inhibitors. Cysteine residues in particular have been exploited for their reactivity toward electrophilic molecules. SAMT-247 is a mercaptobenzamide thioester that covalently acetylates cysteines in the zinc-coordinating domains of the HIV nucleocapsid (NC) protein. We have used mass spectrometry to investigate the mechanism of viral inactivation of NC by SAMT-247, identifying multiple sites of covalent modification that resulted from SAMT reaction. This SAMT-247-promoted reaction leads to loss of zinc binding by the protein, with concomitant loss of protein structure and function. Although it has low cytotoxicity in animal models, recent studies have indicated that it affects other protein targets in uninfected cells, for example leading to increased immune cell functions. We have used global proteomics approaches have been used to better understand other protein targets of SAMT-247 in THP-1 cells. Although minimal effects are observed when unstimulated THP-1 monocyte cells were treated with SAMT-247, many potential targets were identified when the THP-1 cells were stimulated with phorbol 12-myristate 13-acetate/Ionomycin (PMA/Iono) before SAMT-247 treatment. Among the affected proteins, several with zinc-coordinating domains and/or reactive cysteine residues were found. Further study of reaction of SAMT-247 with two potential targets verified that they are modified by the inhibitor. The increased effects of SAMT-247 in stimulated immune cells suggests that this molecule could be developed to target diseases other than HIV.
Lightning Talk
Automatic Blood Protein Enrichment by Magnetic-COF Polymers
Yuanyu Huang, Johns Hopkins University
Abstract: Blood proteome is a highly informative biological fluid, reflecting physiological and pathological states across the entire body. Automated Magnetic-COF workflow achieves deep, reproducible, and scalable blood proteome profiling across plasma, serum, and whole blood, with reduced dominance of high-abundance proteins and improved access to low-abundance species. The platform maintained low variability and broad physicochemical coverage without introducing major enrichment bias, which enabled identification of more than 4000 blood proteins with the throughput of 30 samples per day. Applied to a 110-sample PDAC serum cohort, it delivered stable cohort-scale performance, identified clinically relevant differential proteins, and highlighted biomarker candidates such as APOE and CEACAM5 with promising diagnostic value. Collectively, these findings establish Magnetic-COF–based automation as a robust strategy for high-throughput blood proteomics and translational biomarker discovery in PDAC.
