In 1999, Clardy et al. reported the isolation and structure elucidation of a family of new cyclopeptides from a marine streptomycete CNB-982, called cyclomarins. The major metabolite cyclomarin A showed an interesting activity toward mycobacterium tuberculosis. Detailed studies indicated, that ClpC1, a subunit of a caseinolytic protease, is the actual target of CycA. Cyclomarin also shows antimalaria activity by inhibiting the PfAp3Aase of the protozoan parasite.
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Cyclomarins are cyclic heptapeptides containing four unusual amino acids. New synthetic protocols toward their synthesis have been developed, leading to the synthesis and biological evaluation of three natural occurring cyclomarins. Interestingly, cyclomarins address two completely different targets: Clp C1, a subunit of the caseinolytic protease of Mycobacterium tuberculosis (MTB), as well as PfAp3Ase of Plasmodium falciparum. Therefore, cyclomarins are interesting lead structures for the development of drugs against tuberculosis and malaria.
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