Archive for January 8th, 2024

Macrocyclic peptide antibiotics – now Zosurabalpin – then antibacterial agents based on cyclic D,L-α-peptide architectures.

Monday, January 8th, 2024

Zosurabalbin[1],[2], is receiving a great deal of attention as a new class of antibiotic which can target infections for which current treatment options are inadequate. It is a cyclic peptide and seeing this triggered memory of an earlier such species reported way back in 1995[3],[4]. This octa-peptide (YIJDIE, DOI: 10.5517/cc58gxs) was presumed to function in a novel manner, having linear water channels wide enough to form a molecular nanoscale pipe for a stream of water molecules to flow along. When inserted into the bacterial cell membrane via its lipophilic sidechains, it drained the bacterium of its cell water within seconds, thus killing it. A 3D model shows the effect very clearly.

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References

  1. C. Zampaloni, P. Mattei, K. Bleicher, L. Winther, C. Thäte, C. Bucher, J. Adam, A. Alanine, K.E. Amrein, V. Baidin, C. Bieniossek, C. Bissantz, F. Boess, C. Cantrill, T. Clairfeuille, F. Dey, P. Di Giorgio, P. du Castel, D. Dylus, P. Dzygiel, A. Felici, F. García-Alcalde, A. Haldimann, M. Leipner, S. Leyn, S. Louvel, P. Misson, A. Osterman, K. Pahil, S. Rigo, A. Schäublin, S. Scharf, P. Schmitz, T. Stoll, A. Trauner, S. Zoffmann, D. Kahne, J.A.T. Young, M.A. Lobritz, and K.A. Bradley, "A novel antibiotic class targeting the lipopolysaccharide transporter", Nature, vol. 625, pp. 566-571, 2024. http://dx.doi.org/10.1038/s41586-023-06873-0
  2. S. Hawser, N. Kothari, T. Valmont, S. Louvel, and C. Zampaloni, "2131. Activity of the Novel Antibiotic Zosurabalpin (RG6006) against Clinical Acinetobacter Isolates from China", Open Forum Infectious Diseases, vol. 10, 2023. http://dx.doi.org/10.1093/ofid/ofad500.1754
  3. M.R. Ghadiri, K. Kobayashi, J.R. Granja, R.K. Chadha, and D.E. McRee, "The Structural and Thermodynamic Basis for the Formation of Self‐Assembled Peptide Nanotubes", Angewandte Chemie International Edition in English, vol. 34, pp. 93-95, 1995. http://dx.doi.org/10.1002/anie.199500931
  4. S. Fernandez-Lopez, H. Kim, E.C. Choi, M. Delgado, J.R. Granja, A. Khasanov, K. Kraehenbuehl, G. Long, D.A. Weinberger, K.M. Wilcoxen, and M.R. Ghadiri, "Antibacterial agents based on the cyclic d,l-α-peptide architecture", Nature, vol. 412, pp. 452-455, 2001. http://dx.doi.org/10.1038/35086601

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