Synthesis and Screening of a Combinatorial Peptide Library for Ligands to Target Transferrin: Miniaturizing the Library

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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 … continued below

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vi, 64 p. : ill.

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Brown, Jennifer Marie August 2010.

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This thesis is part of the collection entitled: UNT Theses and Dissertations and was provided by the UNT Libraries to the UNT Digital Library, a digital repository hosted by the UNT Libraries. It has been viewed 838 times. More information about this thesis can be viewed below.

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  • Brown, Jennifer M.

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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.

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vi, 64 p. : ill.

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  • August 2010

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  • Jan. 6, 2011, 6:55 a.m.

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Brown, Jennifer Marie. Synthesis and Screening of a Combinatorial Peptide Library for Ligands to Target Transferrin: Miniaturizing the Library, thesis, August 2010; Denton, Texas. (https://digital.library.unt.edu/ark:/67531/metadc30440/: accessed May 26, 2024), University of North Texas Libraries, UNT Digital Library, https://digital.library.unt.edu; .

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