Redox Potential of Azobenzene as an Amino Acid Residue in Peptides

DOI: 10.1002/cbic.200600495

(Azobenzene Peptides)

Redox Potential of Azobenzene as Amino Acid Residue in Peptides

Cyril Boulègue,[a] Markus Löweneck,[a,b] Christian Renner,[a,b] and Luis Moroder[a]*

[a]        Dr. C. Boulègue, Dr. M. Löweneck, PD Dr. C. Renner, Prof. Dr. L. Moroder

Bioorganic Chemistry

Max-Planck-Institut für Biochemie

Am Klopferspitz 18

82152 Martinsried

Germany

Fax: (+)49-89-8578 2847

E-mail: moroder@biochem.mpg.de

[b]        Present addresses: C. Renner, Deutsche Forschungsgemeinschaft, Kennedyallee 40, D-53175 Bonn; M. Löweneck, Senn Chemicals AG, Guido Senn Str. 1, CH-8157 Dielsdorf.

Supplementary Material: LC-MS characterization of the product distributions upon treatment of the azobenzene-tripeptide with glutathione.

Photochromic compounds that undergo in reversible manner significant structural changes when exposed to light of appropriate wavelength are particularly attractive as molecular switches as they allow storage of information at the molecular level. Of the many chromophores that fulfil this criterion, azobenzene derivatives have become a popular choice in various fields of polymer science, material science, chemistry and, even, life sciences.[1] Indeed by strategic incorporation of this light switch into (bio)polymers photomodulation of one or the other physical, chemical and biochemical property is readily achieved because of its pronounced change in geometry as well as dipole moment upon isomerization of the central diazene double bond.[2] Moreover, minimal photobleaching of this chromophore, high quantum yields and large population differences (cis/trans) achievable as well as the ultrafast isomerization (within picoseconds) are properties that favour the use of azobenzene for inducing responsiveness to light.[2,3] We and others have successfully applied related derivatives as conformational clamps or as amino acid units to restrict the conformational space of cyclic and linear peptides and thus to photocontrol conformational states such as α-helices,[1f,4] β-turns,[1g,5] β-hairpins,[6] as well as tertiary structures.[7] The ultimate aim would be to incorporate this photo-switch into proteins by the most advanced ligation procedures for in vitro and possibly even in vivo induction of “on” and “off” states of proteins involved in vital cellular events. However, for this purpose a serious intrinsic drawback of azobenzene could derive from its possible reduction by the thiols required in the ligation procedures to produce proteins with photo-switchable bioactivities[8] and by the glutathione present in cells at millimolar concentrations (0.5-10 mM).[9]