Photomodulation of conformational states. II. Mono- and bicyclic peptides with (4-aminomethyl)phenylazobenzoic acid as backbone constituent

It has been reported that backbone cyclization of octapeptides with the pho toresponsive (4-aminomethyl)phenylazobenzoic acid imparts sufficient restra ints to induce and stabilize ordered conformations of the peptide backbone in both the cis- and trans-azo-isomers (L. Ulysse, J. Cubillos, and J. Chmi elewski, Journal of the American Chemical Society, 1995, Vol. 117, pp. 8466 -8467). Correspondingly, the active-site octapeptide fragment H-Ala-Cys-Ala -Thr-Cs-Asp-Gly-Phe-OH [134-141] of thioredoxin reductase, with its high pr eference for a 3(10)-helix turn conformation centered on the Thr-Cys sequen ce, was backbone cyclized with this azobenzene moiety in the attempt to des ign a photoresponsive system where the conformational states of the peptide backbone are dictated by the configuration of the azobenzene and can be fu rther modulated by the disulfide bridge. Nuclear magnetic resonance conform ational analysis of the monocyclic compound clearly revealed the presence o f two conformational families in both the cis- and trans-azo configuration. Of the higher populated conformational families, the structure of the tran s-isomer seems like a pretzel-like folding, while the cis-isomer relaxes in to a significantly less defined conformational state that does not exhibit any regular structural elements. Further restrictions imparted by disulfide bridging of the peptide moiety leads to an even better defined conformatio n for the trans-azo-isomer, whereas the cis-isomer can be described as a fr ustrated system without pronounced energy minima and thus with little confo rmational preferences. Our findings would suggest that this photoresponsive peptide template may not be of general usefulness for light-induced confor mational transitions between two well-defined conformational states at leas t under the experimental conditions employed, even int he bicyclic form. Ho wever, trans --> cis isomerization of the bicyclic peptide is accompanied b y a switch from a well-defined conformation to an ensemble of possible conf ormations. (C) 2000 John Wiley & Sons, Inc.