Stereochemistry and Conformation of Skyllamycin, a Non-Ribosomally Synthesized Peptide from Streptomyces sp Acta 2897
2014 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 20, no 17, 4948-4955 p.Article in journal (Refereed) Published
Skyllamycin is a non-ribosomally synthesized cyclic depsipeptide from Streptomyces sp. Acta 2897 that inhibits PDGF-signaling. The peptide scaffold contains an N-terminal cinnamoyl moiety, a -methylation of aspartic acid, three -hydroxylated amino acids and one rarely occurring -hydroxy glycine. With the exception of -hydroxy glycine, the stereochemistry of the amino acids was assigned by comparison to synthetic reference amino acids applying chiral GC-MS and Marfey-HPLC analysis. The stereochemistry of -hydroxy glycine, which is unstable under basic and acidic conditions, was determined by conformational analysis, employing a combination of data from NOESY-NMR spectroscopy, simulated annealing and free MD simulations. The simulation procedures were applied for both R- and S-configured -hydroxy glycine of the skyllamycin structure and compared to the NOESY data. Both methods, simulated annealing and free MD simulations independently support S-configured -hydroxy glycine thus enabling the assignment of all stereocenters in the structure of skyllamycin and devising the role of two-component flavin dependent monooxygenase (Sky39) as S-selective.
Place, publisher, year, edition, pages
Wiley-VCH Verlag , 2014. Vol. 20, no 17, 4948-4955 p.
conformational analysis; NOESY-NMR spectroscopy; peptide antibiotics; skyllamycin; structure elucidation
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-107854DOI: 10.1002/chem.201304562ISI: 000334396900014OAI: oai:DiVA.org:liu-107854DiVA: diva2:727694