• Bioorganic Chemistry and the Origins of Chemical Biology
• 56 min
  1. Biomimetic catalysis

  • Prof. Ronald Breslow
• 50 min
  2. Bioorganic studies of vision

  • Prof. Koji Nakanishi
• 48 min
  3. Perspectives on biological catalysis

  • Prof. Stephen Benkovic
• Nucleic Acids and Drug/Nucleic Acid Interactions
• 41 min
  4. The importance of nucleotide size in the chemistry and biology of DNA

  • Prof. Eric Kool
• 27 min
  5. Site-specifically modified ribosomal RNAs

  • Prof. Christine Chow
• 26 min
  6. Creation of tools for the investigation of oxidative damage to nucleic acids

  • Dr. Mel Bedi
• 48 min
  7. Drug-DNA interactions of the mitomycins

  • Prof. Maria Tomasz
• Protein Function and Cellular Signaling
• 41 min
  8. Chemical synthesis of proteins

  • Prof. Lei Liu
• 55 min
  9. Visualizing and manipulating phosphoinositide and phospholipid signaling

  • Prof. Glenn Prestwich
• 86 min
  10. Phosphoserine/threonine binding domains: molecular integrators of protein kinase signaling in cell cycle control and cancer

  • Dr. Michael Yaffe
• 59 min
  11. Polydactyl zinc finger proteins: software and hardware for genomes

  • Prof. Carlos Barbas
• Peptides, Small-Molecules and Chemical Diversity
• 41 min
  12. Chemical synthesis of peptides and peptide libraries

  • Prof. Victor Hruby
• Proteomics: The Study of Biomolecules and Interactions
• 46 min
  13. Quantitative proteomics

  • Prof. Ruedi Aebersold
• Archived Lectures *These may not cover the latest advances in the field
• 51 min
  14. Chemical protein synthesis: total synthesis of proteins for biological research

  • Prof. Stephen Kent
• 57 min
  15. Solid phase peptide synthesis

  • Prof. Stephen Kent
• 39 min
  16. Mapping small molecule binding sites with phage display technology

  • Dr. Lee Makowski
• 32 min
  17. Tagged library for chemical genetics

  • Dr. Young-Tae Chang
• 30 min
  18. Covalently constrained alpha-helices

  • Dr. Paramjit Arora
• 34 min
  19. SICLOPPS: genetic system for production of backbone cyclized peptides

  • Dr. Sergey Savinov
• 35 min
  20. Probing protein-protein interactions with peptide libraries and arrays

  • Dr. Zhou Songyang

Printable Handouts

PDF

Navigable Slide Index

1. Introduction
2. Goal of described researches
3. How do small molecules bind proteins?
4. Flexible regions in small molecule binding (1)
5. P-loop structures
6. Flexible regions in small molecule binding (2)
7. Methods- phage display
8. Phage display technology
9. Biopanning
10. Phage display - advantages
11. Evaluating library diversity
12. What do we mean by diversity?
13. An intuitive analytical expression of diversity
14. Example (1)
15. Example (2)
16. Example (3)
17. Example (4)
18. The probability to select the same peptide twice
19. RELIC
20. Sequence diversity of proteomes and libraries
21. 12mer libraries with same amino acid distribution
22. Identifying motifs
23. Using diverse populations to identify ATP-BP
24. Consensus sequences as clues to protein function
25. Peptide libraries displayed on phage surface
26. Two ATP substrates used
27. For this to work you need lots of peptides
28. How many P-loops did we select?
29. P-loops are censored from the unselected library!
30. Ratio of ATP-selected peptides
31. Phosphoenolpyruvate carboxykinase
32. Can the method identify ATP-BP?
33. Taxol
34. Taxol- targets and activities
35. Immobilization of taxol through biotinylation
36. One segment of tubulin with high similarity to taxol
37. An alternative means of displaying the results
38. Bcl-3
39. Selected peptides and the flexible loop of Bcl-3
40. Taxol binds to the flexible loop of Bcl-3
41. ELISA data
42. CD spectra
43. Taxol - Bcl-2 interaction
44. Taxol-selected peptides and mdr1/mdr4
45. Taxol binds to loops on the surface of mdr2
46. Taxol's targets
47. Summary
48. Thank you

Topics Covered

• How do you identify the molecular target of a small molecule drug?
• Flexible regions are key players
• P-loop of ATP-binding proteins is an important example
• Can display libraries of flexible peptides on proteins select those that bind to the ligand
• Selection is through an affinity process called biopanning
• Success depends on the diversity of the library
• Diversity depends on how many different peptides are in the library and their relative abundance
• RELIC can be used to calculate the diversity of a library from the sequences of ~100 peptides
• Identification of motifs from a population is easy if the motif is very strong
• Taxol-binding peptides were also identified by phage display and those peptides were used to identify the position on tubulin where taxol is bound and to identify Bcl-2 as a taxolbinding protein
• Significant data from a variety of sources argue that the taxol-Bcl-2 interaction is important to the clinical efficacy of taxol

Links

Series:

• Chemical Biology

Categories:

• Biochemistry
• Methods

Talk Citation

Publication History

• Published on August 14, 2008
• Archived on August 13, 2020

Financial Disclosures

• Dr. Lee Makowski has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.