Combinatorial libraries are used in the search for ligands that bind to target proteins. Fmoc solid-phase peptide synthesis is routinely used to generate such libraries. Microwave-assisted peptide synthesis was employed here to decrease reaction times by 80-90%. Two One-Bead-One-Compound combinatorial libraries were synthesized on 130μm beads (one containing 750 members and the other 16, 807). The use of smaller solid supports would have many important practical advantages including; increased library diversity per unit mass, smaller quantities of library needed to generate hits, and screening could be conducted by using a standard flow cytometer. To this end, a miniaturized peptide library was synthesized on 20 μm beads to demonstrate proof of principle. A small sample from the 16,807-member library was screened against transferrin-AlexaFluro 647, a protein responsible for iron transport in vivo. A number of hits were identified and sequenced using techniques coupling nanomanipulation with nanoelectrospray mass spectrometry.
| Identifer | oai:union.ndltd.org:unt.edu/info:ark/67531/metadc30440 |
| Date | 08 1900 |
| Creators | Brown, Jennifer Marie |
| Contributors | Petros, Robby A., Verbeck, Guido F. |
| Publisher | University of North Texas |
| Source Sets | University of North Texas |
| Language | English |
| Detected Language | English |
| Type | Thesis or Dissertation |
| Format | vi, 64 p. : ill., Text |
| Rights | Public, Copyright, Brown, Jennifer M., Copyright is held by the author, unless otherwise noted. All rights reserved. |
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