Conformation and anion binding properties of cyclic hexapeptides containing L-4-hydroxyproline and 6-aminopicolinic acid subunits.
Two cyclic hexapeptides containing alternating all R and all S configured Ll-(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 10(0) and 10(2) M(-1) in 80% D(2)O/CD(3)OD. 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 10(4) to 10(5) M(-2) in 80% D(2)O/CD(3)OD 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 d(6)-DMSO and methanol/water mixtures a slow conformational equilibrium between two C(3)-symmetrical conformers is observed, and 3 is thus much less preorganized for anion binding than either 1 or 2.
Kubik
Stefan
S
Institut für Organische Chemie und Makromolekulare Chemie, Heinrich-Heine-Universität, Universitätsstrasse 1, D-40225 Düsseldorf, Germany. kubik@uni-duesseldorf.de
Goddard
Richard
R
D000838:Anions; D002942:Circular Dichroism; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D006909:Hydroxyproline / Q000737:chemistry*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry; D010456:Peptides, Cyclic / Q000737:chemistry; D010848:Picolinic Acids / Q000737:chemistry*; D011487:Protein Conformation
D000838:Anions; D010455:Peptides; D010456:Peptides, Cyclic; D010848:Picolinic Acids; D006909:Hydroxyproline; D004121:Dimethyl Sulfoxide