Institut für Pharmazeutische Biologie und Biotechnologie, Heinrich-Heine-Universität, Geb. 26.23, Universitätsstrasse 1, D-40225 Düsseldorf, Germany.
Bioorg Med Chem. 2010 Jul 15;18(14):4947-56. doi: 10.1016/j.bmc.2010.06.012. Epub 2010 Jun 11.
Bioassay guided fractionation of the EtOAc fraction of the sponge Callyspongia aerizusa yielded seven new cytotoxic cyclic peptides callyaerins A-F (1-6) and H (8). Their structures were determined using extensive 1D (1H, 13C and DEPT) and 2D (COSY, HMQC, HMBC, TOCSY, and ROESY) NMR and mass spectral (ESI and HRESI-TOF) data. All compounds were cyclic peptides containing ring systems of 5-9 amino acids and side chains of 2-5 amino acids in length. An unusual (Z)-2,3-diaminoacrylic acid unit provided the template for ring closure and afforded the linkage to the peptidic side chain which was always initiated with a proline moiety. All peptides contained three or more proline residues and the remaining residues were predominantly hydrophobic residues with all amino acids present in the l form. Callyaerins A-F (1-6) and H (8) showed biological activity in antibacterial assays and in various cytotoxicity assays employing different tumour cell-lines (L5178Y, HeLa, and PC12). Callyaerins E (5) and H (8) exhibited strong activity against the L5178Y cell line with ED50 values of 0.39 and 0.48 microM, respectively. On the other hand, callyaerin A (1) showed strong inhibitory properties towards C. albicans.
生物活性导向分离海绵 Callyspongia aerizusa 的乙酸乙酯部位得到七个新的细胞毒性环肽 callyaerins A-F（1-6）和 H（8）。通过广泛的 1D（1H、13C 和 DEPT）和 2D（COSY、HMQC、HMBC、TOCSY 和 ROESY）NMR 和质谱（ESI 和 HRESI-TOF）数据确定了它们的结构。所有化合物均为含有 5-9 个氨基酸的环肽和 2-5 个氨基酸长度的侧链。一个不寻常的（Z）-2,3-二氨基丙烯酸单元为环合提供了模板，并提供了与肽侧链的连接，该侧链总是由脯氨酸部分起始。所有肽均含有三个或更多脯氨酸残基，其余残基主要为疏水性残基，所有氨基酸均呈 L 型。Callyaerins A-F（1-6）和 H（8）在抗菌测定和各种细胞毒性测定中表现出生物活性，采用不同的肿瘤细胞系（L5178Y、HeLa 和 PC12）。Callyaerins E（5）和 H（8）对 L5178Y 细胞系表现出强烈的活性，ED50 值分别为 0.39 和 0.48 μM。另一方面，callyaerin A（1）对 C. albicans 表现出强烈的抑制特性。
