title: Exploring the conformational and biological versatility of β-turn-modified gramicidin S by using sugar amino acid homologues that vary in ring size.
abstract: 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 the cyclo-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.
authors.affiliation: Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands.
authors.forename: Annemiek D
authors.initials: AD
authors.lastname: Knijnenburg
authors.forename: Adriaan W
authors.initials: AW
authors.lastname: Tuin
authors.forename: Emile
authors.initials: E
authors.lastname: Spalburg
authors.forename: Albert J
authors.initials: AJ
authors.lastname: de Neeling
authors.forename: Roos H
authors.initials: RH
authors.lastname: Mars-Groenendijk
authors.forename: Daan
authors.initials: D
authors.lastname: Noort
authors.forename: José M
authors.initials: JM
authors.lastname: Otero
authors.forename: Antonio L
authors.initials: AL
authors.lastname: Llamas-Saiz
authors.forename: Mark J
authors.initials: MJ
authors.lastname: van Raaij
authors.forename: Gijs A
authors.initials: GA
authors.lastname: van der Marel
authors.forename: Herman S
authors.initials: HS
authors.lastname: Overkleeft
authors.forename: Mark
authors.initials: M
authors.lastname: Overhand
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D000606:Amino Sugars; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry*; D002942:Circular Dichroism; D006096:Gramicidin / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D000596:Amino Acids; D000606:Amino Sugars; D000890:Anti-Infective Agents; D009842:Oligopeptides; D006096:Gramicidin