Progress towards understanding antiparallel Beta-sheet structure in aqueous solution /
Two dibenzofuran-based axnino acid residues, namely, 4-
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| Format: | Thesis Book |
| Language: | English |
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[Place of publication not identified] :
[publisher not identified] ;
1994.
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| Online Access: | http://proxy.library.tamu.edu/login?url=http://proquest.umi.com/pqdweb?did=741965951&sid=1&Fmt=2&clientId=2945&RQT=309&VName=PQD |
| Summary: | Two dibenzofuran-based axnino acid residues, namely, 4- (aniinomethyl)-6dibenzofuranethanoic acid (9) and 4-amino-6- dibenzofuranmethanoic acid (10), were prepared in order to compare their physical properties with those of 4-(2- aminoethyl)-6dibenzofuranpropanoic acid (1) so as to further understand the ability of residue 1 to nucleate antiparallel [ ] sheet formation in aqueous solution. FI'-IR and variabletemperature NMR studies reveal that amide analogs of 1 and 9 can adopt intramolecularly hydrogen bonded conformations in nonpolar solvents, whereas amides composed of residue 10 cannot. Spectroscopic studies reveal that linear heptapeptides containing 1 are capable of adopting a fluctuating antiparallel [ ]sheet structure in aqueous solution, whereas residues 9 and 10 are incapable of nucleating a [ ]sheet structure in an otherwise identical peptide sequence. The efficacy of residue 1 as a [ ]sheet nucleator appears to result from a fifteen-membered ring intramolecularly hydrogen bonded hydrophobic cluster conformation which serves as a partial P-sheet template enabling neighboring residues to be added to the growing sheet with a favorable equilibrium constant. The hydrophobic cluster conformation in these heptapeptides is stabilized by the interactions between the dibenzofuran skeleton in 1 and the hydrophobic side chains of the a-amino acid residues flanking 1. In order for residue 1 to nucleate a [ ] sheet structure it must be flanked with hydrophobic a-amino acid residues. Therefore, it is the tripeptide sequence - hydrophobic residue-l-hydrophobic residue- which mediates [ ]sheet nucleation. Cyclic octapeptides containing two units of I have been successfully synthesized and exhibit [ ]sheet structures in aqueous solution as determined by circular dichroism studies. The utilization of conformationally rigid 1 to generate [ ] and rtum mimics has also been achieved as discerned by NMR structural determination. |
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| Item Description: | Vita. "Major Subject: Chemistry". In title, Greek symbol for Beta used. |
| Physical Description: | xiii, 110 leaves : illustrations ; 28 cm. Issued also on microfiche from University Microfilms Inc. |
| Bibliography: | Includes bibliographical references. |