Studies of Peptide Antibiotics. XXXVIII. Synthesis of S,S′-Bi([1-l-hemicystine]-gramicidin S), a Dimerized Analog of Gramicidin S

Abstract

Abstract To investigate the importance of the orientation of side chains of amino acid residues in gramicidin S (GS) for the antibacterial activity, a dimerized analog of GS, namely S,S′-bi([1-l-hemicystine]-GS) (13) was synthesized via removal of p-methoxybenzyl group of [1-S-p-methoxybenzyl-l-cysteine]-GS (12) and subsequent oxidation. Compound 12 showed the same antibacterial activity as GS, whereas 13 was inactive. The resemblance of ORD curves of the two analogs to that of GS suggested the similarity of peptide-backbone structure of these three compounds. Strong activity of 12 was explained by similar conformation of 12 to that of GS. To explain the inactivity of 13, a molecular model was proposed; four hydrophilic side chains are located on surface of the molecule, whereas six hydrophobic are burried.