Peptide synthesis; chemical manipulation of proteins; post-translational modifications; mass spectrometry; research at the interface of biology and chemistry
The primary role of our lab is to provide services to the research community in the areas of organic and analytical chemistry via the Protein Chemistry Technology Center. Specifically we undertake projects that involve peptide and protein chemistry, mass spectrometry and Edman protein sequencing. The services we offer in many instances exceed those available in other institutions. For example, we are able to perform advanced chemical procedures to create and/or modify long polypeptides exceeding 100 residues. We have also developed the technology that allows us to insert chemical sequences and modifications into recombinant proteins, a process termed expressed protein ligation.
Our state-of-the-art mass spectrometry facility offers a range of services including protein identification, post-translational site mapping, intact peptide/protein mass analysis and quantitative studies using iTraq.
In addition to this primary role, we also undertake in-house and collaborative research projects. These usually interface the fields of biology and chemistry, providing greater understanding of biological processes through chemical intervention. We have successfully incorporated site-specific post-translational modifications, such as phosphorylated amino acids, GPI-mimics, fluorescent labels and biotin, into peptides and proteins. Recently we developed chemical molecules that have been shown to enrich low levels of phosphopeptides from complex biological mixtures.
Li Y, Aleryani R, and Ball HL (2011) Characterization of AMPylation on Threonine, Serine, and Tyrosine Using Mass Spectrometry. JASMS in press. Hao YH, Chuang T, Ball HL, Luong P, Li Y, Flores-Saaib RD, Orth K. Characterization of a rabbit polyclonal antibody against threonine-AMPylation. J Biotechnol, 2011, 151(3):251-4.
Kim S, Sun H, Ball HL, Wassmann K, Luo X, Yu H. Phosphorylation of the spindle checkpoint protein Mad2 regulates its conformational transition. Proc Natl Acad SciUSA. 2010 Nov 16;107(46):19772-7.
Aleryani R, Li Y, and Ball, H. L., Chemical synthesis of AMPylated peptides Tetrahedron Letters, 2010; 51:1730-31.
Sun Y, Lu Y, Chen S, Prasad M, Wang X, Zhu Q, Zhang J, Ball H, Feng J, Butler WT, and Qin C. Key proteolytic cleavage site and full-length form of DSPP. J Dental Res, 2010; 89:498-503.
Miller DS, Chirayil S, Ball HL, Luebke KJ: Manipulating cell migration and proliferation with a light-activated polypeptide. ChemBioChem 2009 Feb 13;10(3): 577-84.
Jetton N, Rothberg KG, Hubbard JG, Wise J, Li Y, Ball HL, Ruben L: The cell cycle as a therapeutic target against Trypanosoma brucei: Hesperadin inhibits Aurora kinase-1 and blocks mitotic progression in bloodstream forms. Mol Microbiol 2009 Apr;72(2): 442-48.
Yarbrough ML, Li Y, Kinch LN, Grishin NV, Ball HL, Orth K: AMPylation of Rho GTPases by Vibrio VopS disrupts effector binding and downstream signaling. Science 2009 Jan 9;323(5911): 269-72.