S. Kubik, R. Goddard
Apr 12, 2002
Citations
1
Influential Citations
61
Citations
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abstract
Two cyclic hexapeptides containing alternating all R and all S configured l-(4R/S)-hydroxyproline and 6-aminopicolinic acid subunits are presented, and the influence of the hydroxyl groups on the solubility, conformation, and receptor properties is investigated. Cyclopeptide 2, containing the natural 4R configured hydroxyproline, adopts a conformation similar to that of the unsubstituted peptide 1, which is able to bind anions such as halides and sulfate in aqueous solution. 2 also interacts with these anions, but whereas 1 forms sandwich type 2:1 complexes, in which the anion is bound by two cyclopeptide moieties, 2 forms 1:1 complexes. The stabilities of the halide and sulfate complexes of 2 range between 100 and 102 M−1 in 80% D2O/CD3OD. Complex formation is detectable even in water, but with slightly smaller stability constants. Using this information a quantitative evaluation of the stability of the 2:1 complexes of 1, for which overall stability constants in the order 104 to 105 M−2 in 80% D2O/CD3OD were observed, was made. In contrast to 2, the conformation of 3, containing the non-natural 4S configured hydroxyproline, is strongly affected by the presence of the hydroxyl groups. In d6-DMSO and methanol/water mixtures a slow conformational equilibrium between two C3-symmetrical conformers is observed, and 3 is thus much less preorganized for anion binding than either 1 or 2.