Preparation and metal ion-binding properties of gramicidin S derivatives carrying picolinoyl groups on the ornithine side chains

Abstract

Derivatives of gramicidin S (GS) in which one or both of the two ornithine side chains were picolinoylated were prepared. The dipicolinoyl derivative [Orn(PyCO)^2,2′]GS 1 formed a 1∶1 complex with Cu²⁺ and Zn²⁺ in MeOH, while in the case of the monopicolinoyl derivative [Orn(Boc)²,Orn(PyCO)^2′]GS (2) stepwise formation of 1∶1 and 2∶1 (2∶Cu²⁺) complexes was observed. The formation constant of the Cu²⁺-mediated dimeric species of compound 2 was larger than those of the corresponding linear compounds possessing the partial structure of macrocycle 2. The corresponding tetra-N-methyl derivative [MeOrn(Boc)²,MeOrn(PyCO)^2′,D-MePhe^4,4′]GS 3 also showed lower stability of the 2∶1 complex compared with compound 2, which suggested the presence of a β-sheet-type intermolecular H-bonding interaction between the two molecules of macrocycle 2 in the 2∶1 complex.