Conformational change from antiparallel β‐sheet to α‐helix in a series of depsipeptide, ‐(Leu‐Leu‐Lac)n‐: Syntheses, spectroscopic studies, and crystal structures of Boc‐Leu‐Lac‐OEt and Boc‐(Leu‐Leu‐Lac)n‐OEt (n = 1, 2)

AbstractThe depsipeptides Boc‐Leu‐Lac‐OEt (1) and Boc‐(Leu‐Leu‐Lac)n‐OEt (n = 1, 2) (2 and 3, respectively) (Boc = tert‐butyloxycarbonyl, Lac = L‐lactic acid residue) has been synthesized and studied by crystallographic, CD spectroscopic, and ESI‐MS analyses. In the packing cells, those three compounds adopt β‐strand conformations. Each molecule is linked into a dimer (1) or an infinite assembly (2 and 3) by tight hydrogen bonds of the type NH···OC. Interestingly, the hexamer, 3 shows the first example of antiparallel pleated β‐sheet crystal structure for a depsipeptide molecule. In the packing cells, especially for 3, the ester groups OCO are perpendicularly oriented to the amide groups NHCO and β‐sheet planes to avoid the interaction between O(ester) and OC. Therefore, when the chain length become longer, the O···OC repulsion interaction works as a β‐sheet breaker and hence promotes an α‐helical structure as observed for Boc‐(Leu‐Leu‐Lac)3‐Leu‐Leu‐OEt (4) (Oku et al. Biopolymers 2004, 75, 242–254) and Boc‐(Leu‐Leu‐Lac)n‐OEt (n = 4–6) (5–7) (Katakai et al., Biopolymers 1996, 38, 285–290), in which the O···OC repulsion does not cause significant structural changes in α‐helical main chains. Therefore from the structural and spectroscopic analyses, we have found governing factors for the specificity in the β‐sheet and α‐helix decision in this series of depsipeptides, ‐(Leu‐Leu‐Lac)n‐. © 2007 Wiley Periodicals, Inc. Biopolymers 89: 270–283, 2008.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com