Neurotoxic lipopeptide

Kalkitoxin 335, a novel neurotoxic lipopeptide, was isolated from various Caribbean collections of cyanobacterium L. majuscula and its absolute configuration Z R) was confirmed by chemical synthesis of kalkitoxin... 

The neurotoxic lipopeptide (+)-kalkitoxin was prepared by J.D. White et al., who installed one of the stereocenters via the Myers asymmetric alkylation followed by reductive workup to obtain the enantiopure primary alcohol. 

The neurotoxic lipopeptide kalkitoxin interacts with voltage-sensitive sodium channels in cerebellar granule neurons. Toxicol Lett 158 133-139. doi 10.1016/j. toxlet.2005.03.007... 

Nogle, L.M., Okino, T., and Gerwick, W.H. (2001) Antillatoxin B, a neurotoxic lipopeptide from the marine cyanobacterium Lyngbya majuscula. J. Nat. Prod., 64, 983-985. 

The cyanobacteria produce a plethora of natural products with a wide variety of bioactivities. Many of these compounds are potent toxins and pose a significant hazard to human health and the environment. In freshwater systems, blooms of hepatotoxic cyanobacteria are of greatest concern, while in marine environments neurotoxic species are more problematic. More than 65 neurotoxins have been isolated from cyanobacteria to date. Most notably, these include the highly potent alkaloids anatoxins and saxitoxins (also known as paralytic shellfish toxins, PSTs) however, a variety of other neurotoxic substances have also been isolated from cyanobacteria including the lipopeptides, jamaicamide, antillatoxin, and kalkitoxin, as well as the nonproteinogenic amino acid, p-W-methylamino-L-alanine (BMAA). 

The lipopeptides jamaicamide and kalkitoxin also inhibit voltage-gated sodium channels [9, 10] however, cases of acute human poisonings are rare. Conversely, antillatoxin is a sodium channel activator and one of the most potent ichthyotoxins isolated from nature [11,12]. The neurotoxic amino acid BMAA activates AMP A/ kainate receptors [13], which in chronic cases may contribute to the development of amyotrophic lateral sclerosis-Parkinsonism dementia (for review see [14]). 

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