Membrane proteins make up roughly a third of the human proteome and are over represented in drug targets. The broad long-term goal of this project is to be able to specify and control structure of membrane soluble protein components so that they can be used in therapeutic intervention. Soluble proteins display a bipartite architecture with hydrophilic exteriors and hydrophobic interiors. We have introduced a novel binary patterning scheme for use in membrane environments by use of highly fluorinated amino acids. The work proposed here will focus on understanding fundamental energetics of the interaction of fluorinated amino acids in model systems followed by detailed characterization in aqueous solution. Fluorinated amino acids will also be used to modulate the bioactivity and stability of antimicrobial and therapeutic peptides. Furthermore, designed transmembrane peptides that associate in micelles and phospholipid vesicles will be thermodynamically characterized using disulfide exchange assays and tested for their specificity in choosing binding partners. The information gleaned from the above studies will be used to create ion channel and pore forming bundles within membranes. These assemblies will be further studied using biophysical techniques. The design and characterization studies proposed here should facilitate the construction of membrane transport agents and also allow for activation (or) inhibition of therapeutically relevant membrane embedded proteins.
| Yüksel, Deniz; Bianco, Piero R; Kumar, Krishna (2016) De novo design of protein mimics of B-DNA. Mol Biosyst 12:169-77 |
| Doyle, Jamie R; Harwood, Benjamin N; Krishnaji, Subrahmanian Tarakkad et al. (2014) A two-step strategy to enhance activity of low potency peptides. PLoS One 9:e110502 |
| Doyle, Jamie R; Krishnaji, Subrahmanian T; Zhu, Guangli et al. (2014) Development of a membrane-anchored chemerin receptor agonist as a novel modulator of allergic airway inflammation and neuropathic pain. J Biol Chem 289:13385-96 |
| Krishnamurthy, Vijay M; Raman, Venkata S; Mowery, Richard A et al. (2013) Ligand-induced protein mobility in complexes of carbonic anhydrase II and benzenesulfonamides with oligoglycine chains. PLoS One 8:e57629 |
| Lozano, Mónica M; Liu, Zhao; Sunnick, Eva et al. (2013) Colocalization of the ganglioside G(M1) and cholesterol detected by secondary ion mass spectrometry. J Am Chem Soc 135:5620-30 |
| Clark, Ginevra A; Baleja, James D; Kumar, Krishna (2012) Cross-strand interactions of fluorinated amino acids in ?-hairpin constructs. J Am Chem Soc 134:17912-21 |
| Lorenz, Barbel; Alvarez de Cienfuegos, Luis; Oelkers, Marieelen et al. (2012) Model system for cell adhesion mediated by weak carbohydrate-carbohydrate interactions. J Am Chem Soc 134:3326-9 |
| Molski, Matthew A; Goodman, Jessica L; Craig, Cody J et al. (2010) Beta-peptide bundles with fluorous cores. J Am Chem Soc 132:3658-9 |
| Montclare, Jin Kim; Son, Soojin; Clark, Ginevra A et al. (2009) Biosynthesis and stability of coiled-coil peptides containing (2S,4R)-5,5,5-trifluoroleucine and (2S,4S)-5,5,5-trifluoroleucine. Chembiochem 10:84-6 |
| Akçay, Gizem; Kumar, Krishna (2009) A New Paradigm for Protein Design and Biological Self-Assembly. J Fluor Chem 130:1178-1182 |
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