Acyldepsipeptides

Harrigan, G.G. Harrigan, B.L. Davidson, B.S. (1997) Kailuins A-D, new cyclic acyldepsipeptides from cultures of a marine-derived bacterium. Tetrahedron, 53, 1577-82. 

D., Hellwig, V., Benet-Buchholz, J., Endermann, R., Labischinski, H., and Brotz-Oesterhelt, H. (2006) Medicinal chemistry optimization of acyldepsipeptides of the enopeptin... 

Sass, P., Josten, M., Famulla, K., Schiflfer, G., Sahl, H.G., Hamoen, L., and Brotz-Oesterhelt, H. (2011) Antibiotic acyldepsipeptides activate ClpP peptidase to degrade the cell division protein FtsZ. Proc. Nad. Acad. Sci. U.S.A., 108 (42), 17474-17479. 

Jeon, H., Sung, K.H., Paulsen, H., Rubsamen-Schaeff, H., Brotz-Oesterhelt, H., and Song, H.K. (2010) Structures of ClpP in complex with acyldepsipeptide antibiotics reveal its activation mechanism. Nat. Struct. Mol. Biol, 17 (4), 471-478. 

Another example of small and educated changes resulting in significant improvement of the hit structure is shown below in Eigure 12.10 with the example of the cyclic acyldepsipeptides 17 that have potent antibacterial activity against Gram-positive pathogens [33]. The initial hit structure 17 proved to... 

Carney, D.W., Schmitz, K.R., Truong, J.V., Sauer, R.T., and Sello, J.K. (2014) Restriction of conformational dynamics of the cyclic acyldepsipeptide antibiotics improves their antibacterial activity. Journal of the American Chemical Society, 136, 1922-1929. 

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