Title
Gramicidin S derivatives containing cis- and trans-morpholine amino acids (MAAS) as turn mimetics
Author
Kapoerchan, V.V.
Spalburg, E.
de Neeling, A.J.
Mars-Groenendijk, R.H.
Noort, D.
de Otero, J.M.
Ferraces-Casais, P.
Llamas-Saiz, A.L.
van Raaij, M.J.
van Doorn, J.
van der Marel, G.A.
Overkleeft, H.S.
Overhand, M.
Publication year
2010
Abstract
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 β-hairp0in 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. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA
Subject
Chemistry
Antibiotics
Conformation analysis
Gramicidin s
Peptides
Peptidomimetics
Amino acid, 65072-01-7
Gramicidin, 1405-97-6
Amino Acids
Anti-Bacterial Agents
Dipeptides
Gramicidin, 1405-97-6
Morpholines
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DOI
https://doi.org/10.1002/chem.200902984
TNO identifier
452768
ISSN
0947-6539
Source
Chemistry - A European Journal, 16 (14), 4259-4265
Document type
article