海洋生物毒素研究新进展

海洋生物毒素以其毒性强,结构新颖,药理作用特殊,易合成等特点成为药理学和神经科学的有力工具和新药开发的新来源.本文根据海洋生物毒素的化学结构特征将其大致分为3类:即多肽类毒素,聚醚类毒素,生物碱类毒素等,并对其进行了综述,同时对海洋生物毒素的应用前景进行了展望.     

Conotoxins of the O-superfamily affecting voltage-gated sodium channels

The venoms of predatory cone snails harbor a rich repertoire of peptide toxins that are valuable research tools, but recently have also proven to be useful drugs. Among the conotoxins with several disulfide bridges, the O-superfamily toxins are characterized by a conserved cysteine knot pattern: C-C-CC-C-C. While ω-conotoxins and κ-conotoxins block Ca²⁺ and K⁺ channels, respectively, the closely related δ- and μO-conotoxins affect voltage-gated Na⁺ channels (Na_v channels). δ-conotoxins mainly remove the fast inactivation of Na_v channels and, thus, functionally resemble long-chain scorpion α-toxins. μO-conotoxins are functionally similar to μ-conotoxins, since they inhibit the ion flow through Na_v channels. Recent results from functional and structural assays have gained insight into the underlying molecular mechanisms. Both types of toxins are voltage-sensor toxins interfering with the voltage-sensor elements of Na_v channels. Received 27 December 2006; received after revision 30 January 2007; accepted 19 February 2007     

New O-superfamily conotoxins fromConus striatus inhabited near Chinese Hainan Island

Conotoxins are short peptide-toxins with specific targets and large diversity. They are useful in analgesia, neuroprotection, detection of some kinds of deseases, and receptor and ion channel study. In order to explore the conotoxin resourses of Chinese oceans, rapid amplification of 3′ cDNA ends (RACE) method was utilized to systemically analyze the O-superfamily conotoxin content ofConus striatus inhabited near Chinese Hainan Island. Six new O-superfamily conopeptides were identified, one of which is highly homologous to MVIIA, an N-type calcium channel antagonist.     

Conotoxins and the posttranslational modification of secreted gene products

The venoms of predatory cone snails (genus Conus) have yielded a complex library of about 50–100,000 bioactive peptides, each believed to have a specific physiological target (although peptides from different species may overlap in their target specificity). Conus has evolved the equivalent of a drug development strategy that combines the accelerated evolution of toxin sequences with an unprecedented degree of posttranslational modification. Some Conus venom peptide families are the most highly posttranslationally modified classes of gene products known. We review the variety and complexity of posttranslational modifications documented in Conus peptides so far, and explore the potential of Conus venom peptides as a model system for a more general understanding of which secreted gene products may have modified amino acids. Although the database of modified conotoxins is growing rapidly, there are far more questions raised than answers provided about possible mechanisms and functions of posttranslational modifications in Conus. Received 24 June 2005; received after revision 13 August 2005; accepted 19 September 2005