In an effort to partially mimic the complex interaction between nerve growth
factor (NGF) and its membrane-bound tyrosine kinase A receptor (TrkA), several small
organic molecules with functionalities similar to the side-chains of the amino acid
residues of NGF critical to binding were devised. These molecules were studied
computationally using the program Affinity. Each molecule was individually docked onto
one of the binding sites on TrkA as determined by mutagenesis studies and the x-ray
crystal structure obtained from the Protein Data Bank.
One of the strategies to enhance binding of active peptidomimetics to their target
proteins is to link them together to form either homodimers or heterodimers. However,
these dimers have low solubility in water and mimic only residues that are close together
on the protein. Triethylene oxide- and hexaethylene oxide-based linker molecules were
designed to circumvent these limitations. The increased polarity will improve the watersolubility
and the added lengths, which can be controlled and varied by simple chemical
manipulations, will allow for mimicking critical residues that are farther apart on the
protein.
| Identifer | oai:union.ndltd.org:tamu.edu/oai:repository.tamu.edu:1969.1/4825 |
| Date | 25 April 2007 |
| Creators | Lam, Sang Q. |
| Contributors | Burgess, Kevin |
| Publisher | Texas A&M University |
| Source Sets | Texas A and M University |
| Language | en_US |
| Detected Language | English |
| Type | Book, Thesis, Electronic Thesis, text |
| Format | 1838020 bytes, electronic, application/pdf, born digital |
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