The Effect of Backbone-Heteroatom Substitution on the Folding of Peptides – A Single Fluorine Substituent Prevents a β-Heptapeptide from Folding into a 314-Helix (NMR Analysis)
✍ Scribed by Raveendra I. Mathad; Francois Gessier; Dieter Seebach; Bernhard Jaun
- Publisher
- John Wiley and Sons
- Year
- 2005
- Tongue
- German
- Weight
- 308 KB
- Volume
- 88
- Category
- Article
- ISSN
- 0018-019X
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✦ Synopsis
The b-heptapeptides H-bhVal-bhAla-bhLeu-bhAla(X n )-bhVal-bhAla-bhLeu-OH 3 ± 7 with central 3amino-2-fluoro-, 3-amino-2,2-difluoro-, or 3-amino-2-hydroxybutanoic acid residues (bhAla(X n )) of like and unlike configuration were subjected to a detailed NMR analysis in MeOH solution. For the geminal difluoro and for the F-and OH-substituted derivatives of u-configuration (see 5, 4, and 7, resp.), 14-helices were found, i.e., with axial disposition of the hetero atoms on the helix. The two compounds containing the central l-configured b-amino acid moieties (see 3 and 6) are not helical over the full lengths of the chains; they have quasi-helical termini and a central turn consisting of a ten-membered H-bonded ring (Fig. 2, d ande). Quantum-mechanical calculations with l-and u-AcNH-CHMe-CHF-CONH 2 confirm the observed preference for a conformation with antiperiplanar arrangement of the FÀC and the CO bond. The calculated energy difference between the observed non-helical geometry of this moiety and a hypothetical helical one is 6.4 kcal/mol (Fig. 3).