| 20209520 |
Kapoerchan VV, Spalburg E, de Neeling AJ, Mars-Groenendijk RH, Noort D, Otero JM, Ferraces-Casais P, Llamas-Saiz AL, van Raaij MJ, van Doorn J, van der Marel GA, Overkleeft HS, Overhand M: Gramicidin S Derivatives Containing cis- and trans-Morpholine Amino Acids (MAAs) as Turn Mimetics. Chemistry. 2010 Mar 5;16(14):4259-4265.
The cyclic decapeptide gramicidin S (GS) was used as a model for the evaluation of four turn mimetics. For this purpose, one of the D-Phe-Pro two-residue turn motifs in the rigid cyclic beta-hairpin structure of GS was replaced with morpholine amino acids (MAA 2-5), differing in stereochemistry and length of the side-chain. The conformational properties of the thus obtained GS analogues (6-9) was assessed by using NMR spectroscopy and X-ray crystallography, and correlated with their biological properties (antimicrobial and hemolytic activity). We show that compound 8, containing the dipeptide isostere trans-MAA 4, has an apparent high structural resemblance with GS and that its antibacterial activity against a panel of Gram positive and -negative bacterial strains is better than the derivatives 6, 7 and 9. |
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