A5001598260- Microbial Natural Products and Biosynthesis
- Neuropeptides and Animal Physiology
- Cancer therapeutics and mechanisms
- Antibiotic Resistance in Bacteria
- Steroid Chemistry and Biochemistry
- Employment and Welfare Studies
- Pharmacological Receptor Mechanisms and Effects
- Receptor Mechanisms and Signaling
- Microbial Metabolism and Applications
- Synthetic Organic Chemistry Methods
- Chemical Synthesis and Analysis
UCSF Benioff Children's Hospital
2023
Oakland University
2023
University of California, San Francisco
2023
Johns Hopkins University
2015-2021
Ernest Gallo Clinic and Research Center
2012
Opioid receptors, including the μ- and δ-opioid receptors (MOR DOR), are important targets for treatment of pain. Although there is mounting evidence that these form heteromers, functional role MOR/DOR heteromer remains unresolved. We have designed synthesized bivalent ligands as tools to elucidate heteromer. Our (L2 L4) comprised a compound with low affinity at DOR tethered high MOR, goal producing "tuned affinity" heteromers compared homomers. Here, we show both L2 L4 demonstrate enhanced...
Modular nonribosomal peptide synthetases (NRPSs) are large, multidomain engines of bioactive natural product biosynthesis that function as molecular "assembly lines" in which monomer units selectively bound, modified, and linked a specific order number dictated by their mega-enzyme templates. Recently, condensation domain an NRPS was discovered to carry out the synthesis integrated β-lactam ring from substrate seryl residue during antibiotic biosynthesis. We report here series experiments...
Condensation (C) domains in non-ribosomal peptide synthetases catalyze elongation steps whereby activated amino acid or peptidyl acyl donors are coupled with specific acceptors. In the biosynthesis of β-lactam antibiotic nocardicin A, an unusual C domain converts a seryl tetrapeptide into its pentapeptide product containing integrated ring. While indirect evidence for intermediacy dehydroalanyl species has been reported, here we describe observation elusive enzyme-bound dehydroamino...