Brad R. Green, PhD

Bioanalytical assessment of drug candidates under GLP guidelines. Extraction of compounds from biological matrices by solid phase and liquid phase extraction methods. Assessment of compound stability by LCMS methods.

Discovery and development of nucleic acid tools for the recognition and sequestration of small molecules. Incorporation of nucleic acid derivatives (i.e. XNA) for enzymatic synthesis of metabolically-stable nucleic acid aptamers. Development of nucleic acid biosensors that recognize small molecule toxins/contaminants. In vitro evolution of DNAzymes that exhibit catalytic activities.

Carried out SAR studies of conopeptides to identify important residues for VGSC blockade. Designed and synthesized peptide analogues with enhanced pharmacological activity. Conducted NMR studies to identify structural elements important for VGSC inhibition. Employed two-electrode voltage clamp electrophysiology to assess activities of modified analogues. Utilized recombinant expression for large-scale production of µ-BuIIIB for SAR studies. Developed a high-throughput approach for parallel synthesis and folding of μ-conopeptides.

Research Associate January 2011 - February 2012 Conducted extraction and purification of peptide-rich venoms to discover active components that specifically blocked pain relevant VGSC-subtypes. Coordinated efforts between the University of Utah and Johnson & Johnson PRD for the testing and characterization of active venom components. Graduate Research Assistant August 2007 – December 2010 Designed, synthesized and characterized modified analogues of endogenous neuropeptides for the development of first-in-class therapeutics for the treatment of pain and epilepsy. Developed and carried out assays to assess metabolic stability, bioavailability (logD), and receptor-binding affinity of modified peptide analogs. Undergraduate Research Assistant November 2004 – August 2007 Designed and synthesized μ-SIIIA analogues (polytides) with improved in vivo activity. Conducted comprehensive structure-activity relationship studies to determine amino acid residues responsible for the biological activity of μ-KIIIA. Performed structural characterization of peptide analogues by 1H NMR and developed methods to assess the improved in vitro pharmacology.

Performed synthesis, purification, and folding of cysteine-rich peptides for potential drug development. Conducted studies related to oxidative folding mechanisms of disulfide containing peptides. Explored alternative methods/conditions for oxidative folding of peptides. Performed MALDI-TOF mass spectrometry of modified and unmodified conopeptides.

PhD Thesis Title: "Structural and functional characterization of potent inhibitors of voltage-gated sodium channels from piscivorous members of the genus Conus"

Thesis Title: “Engineering Systemically Bioavailable Analogs of Endogenous Neuropeptides”