Exploring the Conformational and Biological Versatility of β-Turn-Modified Gramicidin S by Using Sugar Amino Acid Homologues that Vary in Ring Size
Annemiek D. Knijnenburg, Adriaan W. Tuin, Emile Spalburg, Albert J. de Neeling, Roos H. Mars-Groenendijk, Daan Noort, Jose M. Otero, Antonio L. Llamas-Saiz, Mark J. van Raaij, Gijs A. van der Marel, Herman S. Overkleeft, Mark Overhand
Chemistry A European Journal
Monobenzylated sugar amino acids (SAAs) that differ in ether ring size (containing an oxetane, furanoid, and pyranoid ring) were synthesized and incorporated in one of the β-turn regions of thecyclo-decapeptide gramicidin S (GS). CD, NMR spectroscopy, modeling, and X-ray diffraction reveal that the ring size of the incorporated SAA moieties determines the spatial positioning of their cis-oriented carboxyl and aminomethyl substituents, thereby subtly influencing the amide linkages with the adjacent amino acids in the sequence. Unlike GS itself, the conformational behavior of the SAA-containing peptides is solvent dependent. The derivative containing the pyranoid SAA is slightly less hydrophobic and displays a diminished haemolytic activity, but has similar antimicrobial properties as GS.
Circular dichroism, Secondary structure, Biochemistry