Construction of neurotoxin database and screening for potential therapeutic agents

Abstract

Snake and scorpion venoms contain many toxins that have important application astherapeutic agents and also as research tools. As a first part of this study, a snake venomneurotoxin (NTX) database was constructed using bioinformatics. Snake NTXs are alarge family of active peptides with considerable sequence homology, but with differentbiological properties. Sequence, functional and structural information on snake venomneurotoxins (svNTXs) are scattered across multiple sources such as journals, books andpublic databases, with very limited functional annotation. Through this study, an on-linedatabase of NTX proteins has been made available at http://sdmc.12r.astar.edu.sg/Templar/DB/snake_neurotoxin. This database can also be found under Swiss-Prot Toxin Annotation Project website http://www.expasy.org/sprot. At present, 272NTXs sequences are available in the database and each sequence contains fully annotatedfunction and literature references. An annotation tool was also incorporated to aidfunctional prediction of newly identified NTXs as an additional resource fortoxinologists. In addition, a classification system based on structure-function andphylogeny relationship derived from 272 NTXs has been proposed and discussed in detailin the thesis.In Traditional Chinese Medicine, the scorpion venom has been used in the treatment ofneuromuscular diseases such as paralysis, epilepsy, apoplexy, hemiplegic and facialparalysis. The screening of these peptides have been carried out using proteomics. Hence,as a second part of this study, a preliminary screening for therapeutic peptides has beencarries out using the gene chip microarray and real-time PCR on the Chinese scorpionvenom. Several interesting peptides have been found to induce changes in expression ofgenes that are involved in neurogenesis in the brain, a finding that is previously unknown.