Llewellyn Lyndon, Negri Andrew, Quilliam Michael
Australian Institute of Marine Science, Marine Biotechnology, PMB 3, Townsville, MC 4810, Australia.
Toxicon. 2004 Jan;43(1):101-4. doi: 10.1016/j.toxicon.2003.10.016.
The paralytic shellfish poison family has been recently extended by the discovery of several analogues possessing a hydoxybenzoate moiety instead of the carbamoyl group one finds in saxitoxin, the parent molecule of this toxin family. We have investigated the potency of these new analogues on a representative isoform of the pharmacological target of these toxins, the voltage gated sodium channel. These toxins were found to have K1's in the low nanomolar range, only slightly less potent than saxitoxin. The hydroxybenzoate group may increase the lipophilicity of these toxins and improve their ability to pass through epithelia and therefore its uptake and elimination in both intoxication victims and animals that bioaccumulate paralytic shellfish toxins.
最近，麻痹性贝类毒素家族得到了扩展，因为发现了几种类似物，它们具有羟基苯甲酸酯部分，而不是在该毒素家族的母体分子石房蛤毒素中发现的氨基甲酰基。我们研究了这些新类似物对这些毒素的药理学靶点——电压门控钠通道的一种代表性亚型的作用效果。发现这些毒素的K1值处于低纳摩尔范围，效力仅略低于石房蛤毒素。羟基苯甲酸酯基团可能会增加这些毒素的亲脂性，并提高它们穿过上皮细胞的能力，从而增强它们在中毒受害者以及生物蓄积麻痹性贝类毒素的动物体内的吸收和消除能力。
