NMR-solution structures of fluoro-substituted β-peptides: A 3 14-helix and a hairpin turn. The first case of a 90° O=C-C-F dihedral angle in an a-fluoro-amide group
Date
2007
Authors
Mathad, R.
Jaun, B.
Flogel, O.
Gardiner, J.
Loweneck, M.
Codee, J.
Seeberger, P.
Seebach, D.
Edmonds, M.
Graichen, F.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Helvetica Chimica Acta, 2007; 90(12):2251-2273
Statement of Responsibility
Raveendra I. Mathad, Bernhard Jaun, Oliver Flögel, James Gardiner, Markus Löweneck, Jeroen D. C. Codée, Peter H. Seeberger, Dieter Seebach, Michael K. Edmonds, Florian H. M. Graichen, and Andrew D. Abell
Conference Name
Abstract
To further study the preference of the antiperiplanar (ap) conformation in -fluoro-amide groups, two -peptides, 1 and 2, containing a (2-F)-3hAla and a (2-F)-2hPhe residue, have been synthesized. Their NMR-solution structures in CD3OH were determined and compared with those of non-F-substituted analogs, 3 and 4a. While we have found in a previous investigation (Helv. Chim. Acta 2005, 88, 266) that a stereospecifically introduced F-substituent in the central position of a -heptapeptide is capable of breaking the 314-helical structure by enforcing the FCCO ap-conformation, we could now demonstrate that the same procedure leads to a structure with the unfavorable ca. 90° FCCO dihedral angle, enforced by the 314-helical folding in a -tridecapeptide (cf. 1; Fig. 4). This is interpreted as a consequence of cooperative folding in the longer -peptide. A F-substituent placed in the turn section of a -peptidic hairpin turn was shown to be in an ap-arrangement with respect to the neighboring CO bond (cf. 2; Fig. 7). Analysis of the non-F-substituted -tetrapeptides (with helix-preventing configurations of the two central 2/3-amino acid residues) provides unusually tight hairpin structural clusters (cf. 3 and 4a; Figs. 8 and 9). The skeleton of the -tetrapeptide H-(R)3hVal-(R)2hVal-(R)3hAla-(S)3hPhe-OH (4a) is proposed as a novel, very simple backbone structure for mimicking -peptidic hairpin turns.