Abstract
In previous studies we have investigated octapeptides backbone‐cyclized by (4‐amino)phenyl azobenzoic acid (APB) or (4‐aminomethyl)phenylazobenzoic acid (AMPB) and containing the active‐site sequence Cys‐Ala‐Thr‐Cys‐Asp from the thioredoxin reductase. The conformational and redox properties of these peptides were strongly dependent on the isomeric state of the azobenzene chromophore. Using the same approach we were successful in constructing photoresponsive ligands for αvβ3 integrin containing the Arg‐Gly‐Asp (RGD) sequence as binding motif. For achieving maximal conformational restriction of the peptide a reduced ring size compared to our previous azobenzene peptides was employed in the cyclic peptide c[Asp‐D‐Phe‐Val‐AMPB‐Lys‐Ala‐Arg‐Gly‐]. Conformational properties of the trans and cis isomers of this peptide in solution were investigated by CD and NMR and were found to differ markedly from the thioredoxin derived azobenzene peptides. In a second peptide, c[Asp‐D‐Phe‐Val‐Lys‐AMPB‐Ala‐Arg‐Gly‐], shifting the position of the chromophore lead to a marked decrease in affinity. With the availability of the x‐ray structure of a cyclic RGD‐pentapeptide bound to αvβ3 integrin (PDB entry 1L5G) modeling of possible bound conformations for trans and cis isomers of both azobenzene peptides was possible. Notably, both peptides in either isomeric form share the same overall conformation in the bound state according to our molecular dynamics simulations. © 2005 Wiley Periodicals, Inc. Biopolymers 77: 304–313, 2005