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Exploring the Conformational and Biological Versatility of β‐Turn‐Modified Gramicidin S by Using Sugar Amino Acid Homologues that Vary in Ring Size
Author(s) -
Knijnenburg Annemiek D.,
Tuin Adriaan W.,
Spalburg Emile,
de Neeling Albert J.,
MarsGroenendijk Roos H.,
Noort Daan,
Otero José M.,
LlamasSaiz Antonio L.,
van Raaij Mark J.,
van der Marel Gijs A.,
Overkleeft Herman S.,
Overhand Mark
Publication year - 2011
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201002895
Subject(s) - gramicidin s , chemistry , ring (chemistry) , stereochemistry , amino acid , oxetane , amide , solvent , turn (biochemistry) , ring size , peptide , gramicidin , organic chemistry , biochemistry , membrane
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.