Synthesis and efficacy of square planar copper complexes designed to nucleate Beta-sheet structure /
The synthesis of four 6,6'-bis(acylamino)-2,2'-bipyridine-
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| Format: | Thesis Book |
| Language: | English |
| Published: |
[Place of publication not identified] :
[publisher not identified] ;
1995.
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| Subjects: | |
| Online Access: | Link to OAKTrust copy http://proxy.library.tamu.edu/login?url=http://proquest.umi.com/pqdweb?did=742535361&sid=1&Fmt=2&clientId=2945&RQT=309&VName=PQD |
| Summary: | The synthesis of four 6,6'-bis(acylamino)-2,2'-bipyridine- based amino acids la-c and 2 are described. These residues, when coordinated to Cu(II), are designed to replace the i + I and i + 2 residues of a []-turn. Amino acids la-c and 2 were incorporated into several different peptides to evaluate their efficacy as 0-sheet nucleators. Matrix assisted laser desorption mass spectroscopy and UV spectroscopy reveal that peptides incorporating these residues bind CU(II) ions under alkaline and acidic conditions with a 1: 1 binding stoichiometry. In an effort to predict the geometry of the metal binding site of peptides containing 0-turn mimics la-c and 2, three model compounds, 19, 20, and 21 were prepared and their crystal structures determined. The crystal structure of 6,6'-bis(phenylacetamide)-2,2-bipyridine (19) suggests that the bipyridine rings of peptides containing these residues should exist in a transoid conformation in the absence of CU(II) ions and other stabilizing forces. The crystal structures of neutral (deprotonated) Cu(II)complex 20 and +2 charged (protonated) Cu(II)-complex 21 suggest that peptides containing residues la-c and 2 bind CU(II) ions under alkaline and acid conditions resulting in a cisoid bipyridine ring conformation with a nearly perfect square planar geometry about the copper atom. Spectroscopic studies on peptides incorporating residue 1B indicate that this residue is capable of nucleating an antiparallel 0-sheet conformation upon binding a single CU(II) ion in basic aqueous buffer. Peptides incorporating residue 2 behave differently than those containing residue 1B in that they are capable of adopting an antiparallel 0-sheet conformation either in the absence or presence of CU(II) ions. The chemical structure of residue 2 is such that the cisoid nucleating conformation may be stabilized by hydrophobic interactions in the absence of transition metal binding. |
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| Item Description: | Vita. "Major Subject: Chemistry". In title, symbol for Greek letter Beta is used. |
| Physical Description: | xi, 102 leaves : illustrations ; 28 cm. Issued also on microfiche from University Microfilms Inc. |
| Bibliography: | Includes bibliographical references. |