Natural Products

Dr. Boyce's lab develops protease-cleavable linkers for peptide prodrugs and antibody-drug conjugates (ADCs) to minimize neutropenia, a common side effect for FDA-approved protease-cleavable ADCs due to premature drug release. The Boyce lab designs biomolecular prodrugs to combat cancer resistance in ccRCC, ovarian, and breast cancers, and focuses on the chemical synthesis, medicinal chemistry optimization, and target evaluation of natural product classes with rare selectivity against cancer.

His lab's research interests focus on protease-activated prodrug development, prodrug linker optimization for cancer therapeutics, biomolecular prodrug development to combat cancer resistance, chemical synthesis of natural product analogs with rare selectivity against cancer, and synthesis of photoaffinity probes for target ID.

Dr. Carcache de Blanco's research interests focus on the discovery of bioactive constituents from natural product sources with potential application in cancer chemoprevention and chemotherapy. She is also interested in the study of botanical dietary supplements and other herbal products used in traditional medicine.

The research in Dr. Fuchs' lab focuses on the design and preparation of bioactive molecules for therapeutic applications against cancer and infectious diseases. His lab utilizes fundamental chemical knowledge and synthetic methodology to facilitate the process of drug discovery and development through the generation of biological probe molecules, the synthesis and modification of lead compounds, and the optimization of drug properties. The overarching goals of these studies are to understand the mechanisms through which small molecules interact with proteins or other biomolecules in the context of disease progression and to improve the potential utility of promising new compounds to help them advance toward the clinic. Recently, the Fuchs lab has collaborated with numerous labs in the areas of natural product drug development for various cancers, the preparation of protein degraders active against leukemia, and HIV-1 capsid and integrase drug development.

My interdisciplinary research program is inspired by the metabolic diversity of microorganisms and the vast array of compounds they produce. Working at the interface of chemistry and biology, my group combines approaches in chemistry, biochemistry, bioinformatics, genetics, and systems biology to discover new natural products, identify bioactivity and mode of action, and to decipher the metabolic basis of their biosynthesis. Ultimately, we seek to translate insights gained from our investigations into solutions for modern day challenges facing human health and the environment. These include new antibiotics to counter drug-resistant pathogens, novel herbicides and biocontrol agents to improve pest management and food security, and engineered biocatalysts to facilitate chemical production by green chemistry and industrial biotechnology.

The research interests of Dr. Kinghorn are on the isolation, characterization and biological evaluation of natural products of higher plant origin, and he has worked in particular on compounds with potential antimicrobial, cancer chemotherapeutic, cancer chemopreventive, sweet-tasting, and bitterness-blocking effects, in addition to the scientific study of botanical dietary supplements.

New natural product sources (new and unidentified fungal and bacterial microorganisms, microbial endophytes, new endemic and medicinal plant species, etc.) contain many undiscovered potential bioactive secondary metabolites that can be used to combat world’s deadly diseases including cancer, malaria, viral infections, and chemoresistance. Their investigation must be prioritized in order to discover new pharmacophores for potential drug candidates. My lab focuses on (1) bioassay-guided isolation, structural elucidation and development of bioactive compounds from natural sources, (2) Drug discovery from Madagascan natural products and (3) drug discovery from ethnomedicine. One of our recent ongoing projects is on the development of insecticides that can be used to control mosquito vector of Zika virus from Madagascan endemic plants.

• Chromatography supported isolation of the minor components from higher plants or other natural organisms.
• Spectroscopic aided structure determination of complex natural products.
• Synthetic modification of bioactive lead compounds.
• Single-crystal X-ray diffraction based determination of conformation and configuration of natural products with multiple chiral centers.
• Bioassay design, development, and performance to evaluate the bioactivities of natural products.