A peptide host that binds a peptide guest affording a beta-sheet structure that subsequently self-assembles : a simple receptor mimic /
A single dibenzofuran template molecule (12) and two tetrapeptides, Val-LysLeu-Lys-dmda, were used to synthesize a host peptide (13) that binds a single tetrapeptide to afford a three-stranded, antiparallel P-sheet structure. Host 13 has an amphiphilic periodicity of two and strongly prefers to bin...
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| Format: | Thesis Book |
| Language: | English |
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[Place of publication not identified] :
[publisher not identified] ;
1995.
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| Subjects: | |
| Online Access: | http://proxy.library.tamu.edu/login?url=http://proquest.umi.com/pqdweb?did=742535211&sid=1&Fmt=2&clientId=2945&RQT=309&VName=PQD |
| Summary: | A single dibenzofuran template molecule (12) and two tetrapeptides, Val-LysLeu-Lys-dmda, were used to synthesize a host peptide (13) that binds a single tetrapeptide to afford a three-stranded, antiparallel P-sheet structure. Host 13 has an amphiphilic periodicity of two and strongly prefers to bind anionic tetrapeptide guests also having an amphiphilic periodicity of two due to the host's cationic character. The host promotes hydrophobic cluster formation involving the dibenzofuran and the flanking valine side chains which seems to serve as a hydrophobic binding site for the carboxylterminus of the guest. Binding of the host 13 to the guest Suc-Glu-Leu-Glu-LeuBzyl (14a) is weak with a Ka of 2.04 x 103 M-1 but is followed by self-association of the host-guest complex into a fibrillar P-sheet structure with an apparent Ka of 2.69 x 106 M-1. Immobilization of the host 13 on a chromatography support makes it possible to evaluate the host-guest interaction in the absence of self-assembly of the host guest complex into the fibrillar structure. Several analogs of the guest have been prepared and analyzed by this chromatographic method in an effort to understand the binding energetics, of the host-guest interaction. Anions effect both the host-guest interactions and the oligomeric P-sheet structure in solution as predicted by the electroselectivity series of anions which bind to the host in competition with the guest. Decreased temperature denaturs the P-sheet assembly in the presence of addedsalt demonstrating the importance of hydrophobic interactions that stabilize the P-sheet structure. Analytical equilibrium ultracentrifugation demonstrates that the host-guest complex assembles into a high molecular weight assembly which sediments from solution in the ultracentrifuge. Electron microscopy of solutions of 13 and 14a reveals the presence of long fibers presumably of cross-P conformation composed of the soluble assembly 13ml4an. |
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| Item Description: | Vita. "Major Subject: Chemistry". In title, symbol for Greek letter beta is used. |
| Physical Description: | xii, 117 leaves : illustrations ; 28 cm. Issued also on microfiche from University Microfilms Inc. |
| Bibliography: | Includes bibliographical references. |