Preparation of tripeptide-bridged dicatechol ligands and their macrocyclic molybdenum(VI) complexes: fixation of the RGD sequence and the WKY sequence of urotensin ii in a cyclic conformation.
Dicatechol ligands were prepared with caprylic acid (6-H(4)) or the naturally occurring RGD (23-H(4)) or WKY sequences (32-H(4)) as spacers. 6-H(4) was prepared by solution-phase amide coupling chemistry, while 16, the precursor of 23-H(4), was obtained by solution-phase and solid-phase preparation. In the latter case, a polystyrene resin with a hydrazine benzoate linker was used as the solid support. The last coupling step was performed simultaneously with cleavage of the peptide from the resin. The protecting groups of 16 were all removed in one step to yield the free ligand 23-H(4). The WKY-bridged derivative 32-H(4) was obtained by a similar solid-phase synthesis followed by deprotection. The reaction of all three ligands with dioxomolybdenum(VI) bis(acetylacetonate) afforded 19-membered metallamacrocycles in which the short peptides are conformationally fixed in a turn-type structure. Hereby, the side-chain functionalities of the peptides do not interfere in the metal complexation.
Albrecht
Markus
M
Institut für Organische Chemie der RWTH, Prof.-Pirlet-Strasse 1, 52074 Aachen, Germany. markus.albrecht@oc.rwth-aachen.de
Stortz
Patrick
P
Runsink
Jan
J
Weis
Patrick
P
D000595:Amino Acid Sequence; D002396:Catechols / Q000138:chemical synthesis* / Q000737:chemistry; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008667:Metalloproteins / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D008982:Molybdenum / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry*; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D014579:Urotensins / Q000737:chemistry*
D002396:Catechols; D008024:Ligands; D008667:Metalloproteins; D009842:Oligopeptides; D014579:Urotensins; C047981:arginyl-glycyl-aspartic acid; D008982:Molybdenum; C029677:urotensin II