圖3. (A ) 頭成 30-45 度角的毒蜥正在咀嚼塑料移液器 (B) 毒液自毒蜥（頭成水平角度）下顎流出 Figure 3. (A) Helodermatid lizard held with its head at a 30-45° angle (below horizontal) and in the process of chewing the bulb (B) A drop of venom comes out from the helodermatid lizard’s lower jaw 目前，在所有從毒蜥毒液中分離出來的治療劑當中， 最為人所知的莫過於用來治療糖尿病的exendin縮氨 酸。這種藥物當中的主要成分是從墨西哥串珠蜥蜴和 希拉毒蜥的exendin-3和exendin-4中發現的。基於 此方面，這些縮氨酸的哺乳類聚集定位和基因數據具 有一定的參考價值。曾有報告指出犬類涎腺含有類似 exendin的免疫反應性，不過研究人員未能在人類涎 腺組織裡發現exendin免疫反應性。通過解剖毒蜥， 不僅可以確定這些縮氨酸在毒液腺裡的分布，還能克 隆這些縮氨酸的基因密碼。不過，由於目前美國和墨 西哥禁止銷售和出口CITES Appendix II 所列明的受 保護瀕危物種，這些問題尚未有進一步解答和進展。 為克服這個難題，我們的研究團隊嘗試了一個頗具挑 戰性的創新方法，從原毒液本身進行克隆，而特別值 Nowadays, the most famous and commonly known therapeutic agents isolated from helodermatid venoms are the exendin peptides in the treatment of diabetes. The lead compounds for this drug were discovered from exendin-3 and exendin-4 of Mexican beaded lizard and Gila monster. In this regard, mammalian localisation and genetic data of these peptides is of some interest. Whereas canine salivary glands are reported to contain exendin-like immunoreactivity, researchers were unable to detect exendin immunoreactivity in human salivary tissue. Anatomic dissection of helodermatid lizards would be very helpful in determining the distribution of these peptides within venom glands, as well as cloning of the genes coding for these peptides. However, as I mentioned earlier, current restrictions on access to these CITES Appendix II protected and endangered species in the US and Mexico delay further clarification of these issues. In order to overcome this issue, my research team thus attempted to obtain this information by a novel and highly-speculative route -- cloning from the crude 個公開發表的毒蜥毒液提取方法以來對該領域最重大 的貢獻。通過蛋白質組和基因組研究，我們對提取自 希拉毒蜥和墨西哥串珠蜥蜴的原毒液進行純化和特性 分析，從而發現了一種新的縮氨酸Helokinestatin。 從希拉毒蜥和墨西哥串珠蜥蜴身上分離出來的 Helokinestatin擁有完全相同的基因排序，這或許 能解釋為何這兩種毒蜥擁有相似的生物學反應，也 表明Helokinestatin可能是由同一祖先毒液縮氨酸 進化而來，或是祖先細微進化演變的結果。此外， Helokinestatin的生物活性也為我們提供了大量寶貴 的資料和新的研究方向，將來或可幫助我們研發出治 療藥物的主要成分。Helokinestatin作為緩激肽B2 受體縮氨酸抑製劑，對毒蜥毒液的總體毒效應起到補 充作用。充分瞭解其作用機理後，或可將其用於製造 舒緩激肽拮抗劑，以控制癌症及類風濕性關節炎患者 因服用消炎藥而出現的相關疾病。當然，此研究加深 了我們對毒液成分及其活性的瞭解，這本身已為我們 提供了非常有價值的資料，為日後醫藥科研提供參考。 on helodermatid venom extraction. Through proteomic and genomic approaches, purification and characterisation of crude venom from Gila monster and Mexican beaded lizard paved the way for the discovery of a hitherto undiscovered peptide -- Helokinestatin. The two identical sequences of isolated Helokinestatin from Gila monster and Mexican beaded lizard probably explain the similar biological actions in both species and also suggest that Helokinestatin evolved from the same ancestral lizard venom peptide or minor evolutionary changes from an ancestor. The biological activity for Helokinestatin also gave us valuable insights and information and avenues to pursue that may lead to the production of lead components for possible therapeutic agents. The role of Helokinestatin as the bradykinin B2 receptor inhibitor peptide supplements the overall toxic effect of the helodermatid venoms. The mechanism of action, once fully understood, could possibly be used in the production of bradykinin antagonists in the management of conditions associated with anti-inflammatory for cancer and rheumatoid arthritis therapies. Nevertheless, the elucidation of venom components and their activity is a valuable resource in itself. A B UMAGAZINE ISSUE 10 63 學院專欄．FACULTY COLUMN
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