Raymond and Beverly Sackler School of Chemistry and Faculty of Exact Sciences, Tel Aviv University, Ramat-Aviv, Tel Aviv 69978, Israel.
Mar Drugs. 2018 Mar 2;16(3):78. doi: 10.3390/md16030078.
During blooms, cyanobacteria produce diverse modified peptides. Among these are the microginins, which inhibit zinc-containing metalloproteases. Ten microginins, microginins KR767 (), KR801(), KR835 (), KR785 (), KR604 (), KR638 (), KR781 (), KR815 (), FR3 (), and FR4 (), were isolated from the extract of a bloom material of sp. (IL-405) collected from the Kishon Reservoir, Israel in the fall of 2009. The structures of the pure compounds were elucidated using 1D and 2D NMR techniques and high-resolution mass spectrometry. The absolute configuration of the chiral centers of the amino acids were determined by Marfey's and advance Marfey's methods and by comparison of ¹H and C NMR chemical shifts of the Ahda derivatives with those of known microginins. These microginins differ in sequence and absolute configuration of the chiral centers of the Ahda moieties and by -methylation of the Ahda amine group and extent of chlorination of the Ahda terminal methyl group. The compounds were evaluated for inhibition of the zinc metalloprotease, aminopeptidase M, and exhibited low- to sub-nanomolar half maximal inhibitory concentration (IC) values.
在水华期间，蓝细菌会产生多种修饰肽。其中包括微囊藻素，它可以抑制含锌金属蛋白酶。从 2009 年秋季以色列基什伦水库采集的 sp.（IL-405）水华材料的提取物中分离得到了 10 种微囊藻素，分别为 microginin KR767 ()、KR801()、KR835 ()、KR785 ()、KR604 ()、KR638 ()、KR781 ()、KR815 ()、FR3 () 和 FR4 ()。采用 1D 和 2D NMR 技术以及高分辨质谱法确定了纯化合物的结构。通过 Marfey 法和高级 Marfey 法以及 Ahda 衍生物的 ¹H 和 C NMR 化学位移与已知微囊藻素的比较，确定了氨基酸手性中心的绝对构型。这些微囊藻素在 Ahda 部分的序列和手性中心的绝对构型、Ahda 胺基的 -甲基化以及 Ahda 末端甲基的氯化程度上存在差异。这些化合物被评估为锌金属蛋白酶、氨肽酶 M 的抑制剂，表现出低至亚纳摩尔的半最大抑制浓度 (IC) 值。
