Peptides in chemistry and biology

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Peptides in chemistry and biology

• Phage display
• Solid phase peptide synthesis and applications of
  synthetic libraries
• Native chemical ligation in protein synthesis

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Scott and Smith, Science v. 249 (1990) p. 386
or
SS
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R4
R2
R3
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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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Solid phase peptide synthesis
100-500 µ
500 nm
15 Å
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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

• 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

• Directed deletions, point mutations
• Gene silencing (siRNA)
• Knock-out mice

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3a. Forward chemical genetics
Mayer et al., Science (1999) v. 286 pp. 971 - 974
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control
monastrol
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Target ID the candidate approach
http//mc11.mcri.ac.uk/wrongtrousers.html Kinesin
movies
http//www.proweb.org/kinesin/
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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.