Laboratory of Biophysics Brief overview I.Computational Biophysics Pastor, Venable, Skibinsky II.Mass spectroscopy & Protein Chemistry Boykins III.Spectroscopy.

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Presentation transcript:

Laboratory of Biophysics Brief overview I.Computational Biophysics Pastor, Venable, Skibinsky II.Mass spectroscopy & Protein Chemistry Boykins III.Spectroscopy Freedberg, Norris, Negin IV.NMR Theory Bull

Characterization of: proteins and peptides carbohydrates and DNA membranes and micelles vaccines, blood & therapeutics adjuvants & delivery systems repeat units, Mening. B capsule polysaccharide DPPC lipid bilayer Human Hemoglobin

Characterization of: proteins and peptides carbohydrates and DNA membranes and micelles Using: mass spec: Maldi-Tof, Quadrapole Ion Trap and Quadrapole-Tof NMR: 300, 500 and 700 MHz Light Scattering: multiangle laser LS interfaced with HPLC Molecular Modeling: local cluster & graphics workstations High-tech, Center-wide, expert users required, $$

Primary Review Responsibilities: LAL test kitsPastor & Boykins AdjuvantsBull, Pastor & Venable Consultations/Support: Protein/peptide chemistryBoykins Mass spec Boykins NMR Freedberg, Norris & Bull Light Scattering Norris Statistics of lot releasePastor & Bull Computers/modelingVenable & Pastor

Four possibilities for product approval/lot release: good product passes good product fails bad product fails bad product passes

Four possibilities for product approval/lot release: good product passes no problem bad product failsno problem

Four possibilities for product approval/lot release: good product failsproblem for manufacturer (manufacturer’s risk) bad product passesproblem for consumer (consumer’s risk) Better characterization improves products/tests, reduces risks

Laboratory Presentations Pastor:Computer Simulation of Membranes Freedberg: NMR Spectroscopy of Carbohydrates Norris: Light Scattering of Polysaccharides and Proteins Bull: Theory and Experiment of NMR Relaxation Venable: Computer Simulation of Carbohydrates and Proteins Boykins: Mass Spectroscopy, Protein Chemistry Origin of preservative effects of trehalose Conformation of carbohydrates using Residual Dipolar Coupling Meningococcal conjugate vaccines/Gates Foundation Direct determination of H-bond in peptides/carbohydrates Conformation of Mening. B capsule polysaccharide Multiple peptide conjugates/malaria & anthrax vaccines

Exciting Result Since Site Visit Collaboration with Laboratory of Biochemistry and Vascular Biology, Division of Hematology. Problems with polymerized hemoglobin blood substitutes Applied: mass spec, molecular modeling, light scattering oxidized raffinose cross-links - supposed to react with lys, - but also bind to  93cys near heme pocket - prevents T-> R transition - accelerates iron release and heme degradation reduced functionality/toxicity

Exciting Result Since Site Visit Collaboration with Laboratory of Biochemistry and Vascular Biology, Division of Hematology. Problems with polymerized hemoglobin blood substitutes Applied: mass spec, molecular modeling, light scattering “O-Raffinose cross-linked hemoglobin lacks site-specific chemistry in the central cavity: structural and functional consequences of β93Cys modification”, Robert Boykins, Paul Buehler, Yiping Jia, Richard Venable, and Abdu Alayash Proteins: Structure, Function, and Bioinformatics (in press) “Structural and functional characterization of glutaraldehyde polymerized bovine hemoglobin and its isolated fractions” Paul Buehler, Robert Boykins, Yiping Jia, Scott Norris, Darón Freedberg and Abdu Alayash, submitted to Analytical Chemistry.