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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.

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Presentation on theme: "Peptides in chemistry and biology 1.Phage display 2.Solid phase peptide synthesis and applications of synthetic libraries 3.Native chemical ligation in."— Presentation transcript:

1 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

2 R1R1 R3R3 R2R2 R4R4 or SS R1R1 R2R2 R3R3 R4R4 Scott and Smith, Science v. 249 (1990) p. 386

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8 Fuzeon

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10 Science v. 271 p. 1854 (1996)

11 Helical Wheels - to determine amphilphilicity

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14 Native chemical ligation --Steve Kent

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17 100-500 µ 500 nm 15 Å Solid phase peptide synthesis

18 =

19 Fmoc Solid Phase Peptide Synthesis

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21 Gramicidin S - a cyclic peptide antibiotic

22 Split pool synthesis

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24 Positional scanning

25 How to identify kinase substrates? kinase Signal output Positional scanning library

26 Cantley et al. JBC v. 272 (1997) p. 952 PKC isoforms

27 Wash, sequence bound peptides

28 Results

29 Approaches to the study of protein function 1.Biochemistry 2.Genetics 3.Pharmacology http://bio.research.ucsc.edu/people/kellogg/

30 Approaches to the study of protein function 1.Biochemistry - requires cell-free assay

31 2a. Forward genetics mutagenize Screen for interesting phenotype Trace phenoptype to mutation

32 2b. Reverse genetics a.Directed deletions, point mutations b.Gene silencing (siRNA) c.Knock-out mice

33 Mayer et al., Science (1999) v. 286 pp. 971 - 974 3a. Forward chemical genetics

34 control + monastrol

35 http://mc11.mcri.ac.uk/wro ngtrousers.html Kinesin movies http://www.proweb.org/ kinesin/ Target ID: the candidate approach

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38 Reverse Chemical Genetics Kevan Shokat Curr. Op. Chem. Biol v. 5 p. 360 (2001)

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46 Ellman, et al.


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