周宏農Chou, Hong-NongHong-NongChou2006-07-262018-07-062006-07-262018-07-062005-07-31http://ntur.lib.ntu.edu.tw//handle/246246/20571Eight naturally purified microcystins (MCs), including MC-LR, MC-FR, MC-WR, MC-RR, [D-Asp3] MC-FR, [D-Asp3] MC-WR, [D-Asp3] MC-RR and [Dha7] MC-RR were utilized to determine the effects of amino acid substitutions and modifications on the MC-induced phosphatase inhibitory activity and animal toxicity. It was found that the replacement of the non-polar amino acid L-leucine at the second position of these heptacyclic peptide toxins by a polar L-arginine greatly reduced their animal toxicities and inhibitory activities against protein phosphatase 1 (PP-1) and 2A (PP-2A). Demethylation of methyldehydroalanine at the seventh amino acid position of MC-RR showed the least animal toxicity and phosphatases inhibition. The loss of methyl group on the common methylaspartic acid (MeAsp) at the third position of MCYST-FR, MCYST-WR and MCYST-RR did not alter their toxicity levels, but significantly reduced their activities in PP-1 inhibition. It suggests that the methyl group on MeAsp is essential in PP-1 inhibition for MCs. However, such a tendency was not observed in the assay of PP-2A activity. Comparing the LD50 of the mouse toxicity assay and IC50 of the PP-1 and PP-2A inhibition assay of eight forms of microcystins by linear correlation, it was clearly demonstrated that the MC-induced toxicity is much more related to the inhibition of PP-2A than PP-1. These results suggest that PP-2A inhibition plays a major role in the MC-induced toxicity.application/pdf344501 bytesapplication/pdfzh-TW國立臺灣大學漁業科學研究所journal articlehttp://ntur.lib.ntu.edu.tw/bitstream/246246/20571/1/932313B002059.pdf