CHAPTER 5 - BINDING
E: MODERN METHODS IN DRUG DEVELOPMENT
BIOCHEMISTRY - DR. JAKUBOWSKI
Learning Goals/Objectives for Chapter 5E: After class and
this reading, students will be able to
- describe the basis for the following methods used to design
- combinatorial drug development
- computer-aided design
- in situ click chemistry
- describe drugs that target specific
- describe the benefit of drugs that
- are mutivalent
- perturb equilibrium
E11. Links and References
from the University of Alberta
database is a unique bioinformatics and cheminformatics resource that
combines detailed drug (i.e. chemical, pharmacological and pharmaceutical)
data with comprehensive drug target (i.e. sequence, structure, and pathway)
Mother of All Databases - largest collection of well resolved protein
crystal structures with clearly identified biologically relevant ligands
annotated with experimentally determined binding data
- Moellering, R. et al. Direct inhibition of the NOTCH
transcription factor complex. Nature 462, 171 and 182 (2009)
- Keiser, M. et al. Predicting new molecular targets for known drugs.
Nature 462, 167 and 175 (2009)
- Oh, P. et al. Subtractive proteomic mapping of the endothelial
surface in lung and solid tumours for tissue-specific therapy. Nature.
429, pg 629 (2004)
- Dumoulin, M. et al. A camelid antibody fragment inhibits the
formation of amyloid fibrils by human lysozyme. Nature, 424, pg 783
- Huang, D. et al. Crystal structure of NF-κB (p50)2 complexed to a
high affinity RNA aptamer. Proc. Natl. Acad. Sci. USA. 100, pg 9268
- Sanchez, I. et al. Pivotal Role of oligomerization in expanced
polyglutamine neurodegenerative disorders. Nature. 421, pg 373, (2003)
- Hammarstrom, P. et al. Prevention of Transthyretin Amyloid Disease
by changing protein misfolding energetics. Science. 299, pg 713 (2003)
- Rusconi, C. et al. RNA apatmaers as reversible antagonists of
coagulation factor IXA. Nature. 419, pg 90, 23 (2002)
- Zasloff. Antimicorbial peptides of multicellular organisms. Nature.
415, pg 389 (2002)
- RNA Interference: The Short Answer (blocking mRNA). Nature. 411 pg
- Fernandez-Lopez et al. Rings of Destruction. (Cyclic peptides as
drugs). Natuare. 412 pg 392, 452 (2001)
- Small but mighty timekeepers. (small RNA inhibition of translation)
Nautre. 408, pg 37 (2000)
- Shokat et al. A Chemistry Set for Life. (Chemical genetics:
inhibitors designed for specific gene products)*** Nature 407, pg 282,
- Clark et al. Molecular Switches in Metastasis. Nature. 406. pg 466,
- Root et al. Protein Design of an HIV-1 Entry Inhibitor. Science.
291, pg 884 (2001)
- Tyler et al. Peptide nucleic acids
targeted to the neurotensin receptor and administered i.p. cross the
blood-brain barrier and specifically reduce gene expression .
PNAS, Vol. 96, Issue 12, 7053-7058, June 8, 1999.
- Interfering with Gene Expression (silencing at the mRNA level).
Science. 288, pg 1370 (2000)
- Gellman et al. Slaying Bacteria with β-peptides. Nature. 404, pg
- RNA interference (RNAi by short RNAs that demonstrate
transcriptional silencing). Science. 287, pg 2431, 2494 (2000)
- Evans and Relling. Pharmocogenomics: Translating function genomics
into rational therapeutics. Science. 286, pg 487 (1999)
- Kiessling, L et al.
Synthetic multivalent ligands in the exploration of cell-surface
Current Opinion in Chemical Biology, 4, pg696 (2000)
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