| Gamma2-, gamma3-, and gamma(2,3,4)-amino acids, coupling to gamma-hexapeptides: CD spectra, NMR solution and X-ray crystal structures of gamma-peptides. | |
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MedLine Citation:
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PMID: 11855705 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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There are numerous possible gamma-amino acids with different degrees of substitution and with various constitutions and configurations. Of these the gamma4- and the like- and unlike-gamma(2,4)-amino acids have been previously used as building blocks in gamma-peptides. The synthesis of gamma2-, gamma3-, and gamma(2,3,4)-peptides is now described. The corresponding amino acids have been prepared by Michael addition of chiral N-acyl-oxazolidinone enolates to nitro-olefins, with subsequent reduction of the NO2 to NH2 groups. Such additions to E-2-methyl-nitropropene provide (2R,3R,4R)-2-alkyl-3-methyl-4-amino-pentanoic acid derivatives (9, 10, 11). Stepwise coupling and fragment coupling lead to gamma-di-, tri-, and hexapeptides (12-23), which were fully characterized. The crystal structures of one of the gamma-amino acids (2,3-dimethyl-4-amino-pentanoic acid x HCl, 9a), of a gamma(2,3,4)-di- and a gamma(2,3,4)-tetrapeptide (20, 22) are described, and the NMR solution structure in MeOH of a gamma(2,3,4)-hexapeptide (3) has been determined (using TOCSY, COSY, HSOC, HMBC and ROESY measurements and a molecular dynamics simulated-annealing protocol). A linear conformation (sheet-like), a novel (M) helix built of nine-membered hydrogen-bonded rings, and (M) 2.6(14) helices have thus been identified. NMR measurements at different temperatures (298-393 K) and H/D-exchange rates obtained for the gamma(2,3,4)-hexapeptide are interpreted as evidence for the stability of the 2.6(14) helix (no "melting") and for its non-cooperative folding mechanism. CD Spectra of the gamma-peptides have been measured in MeOH and CH3CN, indicating that only the protected and unprotected gamma(2,3,4)-hexapeptide is present as the 2.6(14) helix in solution. The structures of the gamma2- and gamma3-hexapeptides (1, 2) could not be determined. |
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Authors:
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Dieter Seebach; Meinrad Brenner; Magnus Rueping; Bernhard Jaun |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Chemistry (Weinheim an der Bergstrasse, Germany) Volume: 8 ISSN: 0947-6539 ISO Abbreviation: Chemistry Publication Date: 2002 Feb |
Date Detail:
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Created Date: 2002-02-21 Completed Date: 2002-11-04 Revised Date: 2009-08-04 |
Medline Journal Info:
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Nlm Unique ID: 9513783 Medline TA: Chemistry Country: Germany |
Other Details:
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Languages: eng Pagination: 573-84 Citation Subset: IM |
Affiliation:
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Laboratorium für Organische Chemie der Eidgenössischen Technischen Hochschule Zürich, ETH Hönggerberg, Switzerland. seebach@org.chem.ethz.ch |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acids
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chemistry* Circular Dichroism Crystallography, X-Ray Hydrogen Bonding Nuclear Magnetic Resonance, Biomolecular Oligopeptides / chemical synthesis*, chemistry Protein Structure, Secondary / drug effects Solvents / pharmacology gamma-Aminobutyric Acid / analogs & derivatives, chemistry* |
| Chemical | |
Reg. No./Substance:
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0/Amino Acids; 0/Oligopeptides; 0/Solvents; 56-12-2/gamma-Aminobutyric Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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