Microcystins: Synthesis and structure–activity relationship studies toward PP1 and PP2A. Issue 6 (15th March 2018)

• Record Type: Journal Article
• Authors: Fontanillo, Miriam; Köhn, Maja
• Is Part Of: Bioorganic & medicinal chemistry. Volume 26:Issue 6(2018)
• Page Start: 1118
• Page End: 1126
• Publication Date: 2018-03-15
• Subjects: Adda (2S, 3S, 8S, 9S)-3-amino-9-methoxy-2, 6, 8-trimethyl-10-phenyldeca-4, 6-dienoic acid -- Amba (2S, 3S)-3-amino-2-methylbutanoic acid -- Boc tert-butoxycarbonyl -- BOP benzotriazol-1-yloxy-tris-dimethylaminophosphoniumhexafluoro phosphate -- Cbz carboxybenzyl -- DCC N, N′-dicyclohexylcarbodiimide -- DIFMUP 6, 8-difluoro-4-methylumbelliferyl phosphate -- DIPEA diisopropylethylamine -- DMF N, N-dimethylformamide -- ELSD Evaporative Light Scattering Detector -- equiv equivalent -- Fmoc 9-fluorenylmethoxycarbonyl -- HATU O-7-azabenzotriazol-1-yl-1, 1, 3, 3-tetramethyluroniumhexafluoro phosphate -- HBTU 2-(1H-benzotriazol-1-yl)-1, 1, 3, 3-tetramethyluroniumhexafluoro phosphate -- HOAc acetic acid -- HOAT 1-hydroxy-7-azabenzotriazole -- HOBT 1-hydroxybenzotriazole -- HPLC high performance liquid chromatography -- IC50 half maximal inhibitory concentration -- MBHA 4-methylbenzhydrylamine -- MC microcystin -- Mdha N-methyldehydroalanine -- Mdhb N-methyl dehydrobutyric acid -- MeLan N-methyllanthionine -- Pfp pentafluorophenyl -- PhFl phenylfluorenyl -- pNPP para-nitrophenyl phosphate -- PPIs protein-protein interactions -- PPPs phosphoprotein phosphatases -- PP1 protein phosphatase 1 -- PP2A protein phosphatase 2A -- Pr propyl -- PSTPs protein Ser/Thr phosphatases -- PTKs protein tyrosine kinases -- PyOAP (7-azabenzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate -- SmI2 sodium naphthalide -- TFA trifluoroacetic acid -- TFE trifluoroethanol -- TIPS triisopropylsilane -- UPLC ultra performance liquid chromatography; Microcystin -- Protein phosphatases -- Inhibitors -- Structure-activity relationship -- Medicinal chemistry; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2017.08.040
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Microcystins are highly toxic cyanotoxins responsible for plant, animal and human poisoning. Exposure to microcystins, mainly through drinkable water and contaminated food, is a current world health concern. Although it is quite challenging, the synthesis of these potent cyanotoxins, analogs and derivatives helps to evaluate their toxicological properties and to elucidate their binding mechanisms to their main targets Protein Phosphatase-1 (PP1) and -2A (PP2A). This review focuses on synthetic approaches to prepare microcystins and analogs and compiles structure–activity relationship (SAR) studies that describe the unique features of microcystins that make them so potent.