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Peptides in chemistry and biology 1.Phage display 2.Solid phase peptide synthesis and applications of synthetic libraries 3.Native chemical ligation in protein synthesis
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R1R1 R3R3 R2R2 R4R4 or SS R1R1 R2R2 R3R3 R4R4 Scott and Smith, Science v. 249 (1990) p. 386
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Fuzeon
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Science v. 271 p. 1854 (1996)
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Helical Wheels - to determine amphilphilicity
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Native chemical ligation --Steve Kent
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100-500 µ 500 nm 15 Å Solid phase peptide synthesis
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=
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Fmoc Solid Phase Peptide Synthesis
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Gramicidin S - a cyclic peptide antibiotic
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Split pool synthesis
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Positional scanning
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How to identify kinase substrates? kinase Signal output Positional scanning library
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Cantley et al. JBC v. 272 (1997) p. 952 PKC isoforms
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Wash, sequence bound peptides
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Results
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Approaches to the study of protein function 1.Biochemistry 2.Genetics 3.Pharmacology http://bio.research.ucsc.edu/people/kellogg/
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Approaches to the study of protein function 1.Biochemistry - requires cell-free assay
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2a. Forward genetics mutagenize Screen for interesting phenotype Trace phenoptype to mutation
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2b. Reverse genetics a.Directed deletions, point mutations b.Gene silencing (siRNA) c.Knock-out mice
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Mayer et al., Science (1999) v. 286 pp. 971 - 974 3a. Forward chemical genetics
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control + monastrol
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http://mc11.mcri.ac.uk/wro ngtrousers.html Kinesin movies http://www.proweb.org/ kinesin/ Target ID: the candidate approach
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Reverse Chemical Genetics Kevan Shokat Curr. Op. Chem. Biol v. 5 p. 360 (2001)
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Ellman, et al.
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