Puwainaphycins – when your heart skips a beat – University of Copenhagen

NaToxAq > Toxin of the week > Puwainaphycins

22 May 2018

Puwainaphycins – when your heart skips a beat

Natural toxin

Puwainaphycins represent a novel class of cyclic (lipo-) peptides that have cardioactive functions.

The ability to produce puwainaphycins has been reported in at least two genera of cyanobacteria: Cylindrospermopsis and Anabaena. Alike many non-essential (secondary) metabolites, puwainaphycins are synthesized by non-ribosomal mixed peptide/ketide synthetases. The modular organization of these “conveyor belt factories” accounts for the incorporation of unusual amino acids and carbonic acids and for the diversity in structure observed1,2.

Structure of Puwainaphycin B. Click for larger image

Investigations into the biological activity revealed activity on mouse heart-tissue by alteration of intracellular calcium (Ca2+) levels, which is the main electrophysiological actor in the heart muscle and responsible for contractions of the heart, hence for the heartbeat3,4.

The biological function on the depolarization of heart tissue makes puwainaphycins very interesting compounds for pharmacological research and potential applications, similar to digoxin from the plant Digitalis purpurea, e.g. for the treatment of heart attacks and arrhythmias.

SMILES (Puwainaphycin B): CCCCC(=O)CCCCCCCCCC(C)C1C(C(=O)NC(C(=O)NC(=CC)C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NCC(=O)NC(C(=O)N(C(C(=O)N2CCCC2C(=O)N1)CC(=O)N)C)C(C)OC)CCC(=O)N)C(C)C)C(C)O)C(C)C)O

References:

  1. Gregson, J. M., Chen, J.-L., Patterson, G. M. L. & Moore, R. E. Structures of puwainaphycins A–E. Tetrahedron 48, 3727–3734 (1992).
  2. Mareš, J., Hájek, J., Urajová, P., Kopecký, J. & Hrouzek, P. A Hybrid Non-Ribosomal Peptide/Polyketide Synthetase Containing Fatty-Acyl Ligase (FAAL) Synthesizes the β-Amino Fatty Acid Lipopeptides Puwainaphycins in the Cyanobacterium Cylindrospermum alatosporum. PLoS One 9, e111904 (2014).
  3. Hrouzek, P. et al. The Cyanobacterial Cyclic Lipopeptides Puwainaphycins F/G Are Inducing Necrosis via Cell Membrane Permeabilization and Subsequent Unusual Actin Relocalization. Chem. Res. Toxicol. 25, 1203–1211 (2012).
  4. Moore, R. E. et al. Puwainaphycin C, a cardioactive cyclic peptide from the blue-green alga Anabaena BQ-16-1. Use of two-dimensional carbon-13-carbon-13 and carbon-13-nitrogen-15 correlation spectroscopy in sequencing the amino acid units. J. Am. Chem. Soc. 111, 6128–6132 (1989).

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