The Column - December 2008 - (Page 23)

December 2008 www.thecolumn.eu.com The Column Q&A Animal Pharma Professor Chris Shaw from Queens University, Belfast spoke to Alasdair Matheson about the role of biologically-active peptides from reptile and amphibian venom in drug discovery and the techniques used to detect these compounds. Why are you investigating peptides in reptile, amphibian and arthropod venoms? Venoms are highly-evolved and naturally-selected cocktails of biologically-active peptides/proteins and other molecules, each of which plays a defined role through interaction with highly-specific molecular targets. It is this “cruise missile” type of precision and optimization of structure for function that renders these molecules intriguing models for the drug discovery scientist, in terms of both new lead discovery and new target identification. Many of the component peptides may either represent novel site-substituted analogues of known actives or may be entirely novel structures to science. In each instance, with the insight of creative pharmacologists and cell biologists focused on an array of discrete research end-points, a plethora of new information can be generated, some of which may be crucial in the development of novel therapeutic approaches. When it comes to understanding the molecular basis of disease, you can never know too much about the enemy. Additionally, the primary structural novelty of such peptides presents the peptide chemist with a major problem in tandem mass spectrometric “de novo” sequencing, that is, peptide sequencing performed without prior knowledge of the amino acid sequence. For humans and other so-called “model species” the translated genomes can be trawled on-line for matches, but there are no on-line reference bases available for frogs or snakes. If MS–MS fragmentation only generated - and -ions there would not be a problem, but this is rarely the case. Manual de novo sequencing is possible in some cases, but it is labour-intensive and requires specialised skill sets and experience."Overcoming this problem has attracted the attention of manufacturers who deem these model systems as ideal for both hardware and software developments or modifications. How do you select which creatures to investigate and where and how do you collect the samples? In this area of research it helps to have a multi-disciplinary mind, a large cerebral database of appropriate knowledge ranging from analytical chemistry technology, natural history, molecular pathology, bioinformatics, etc., and — to a large extent — the ability to withstand the wiles of less creative scientific peers! All of these are part of the decision making process. However, we have an axiom — that the only rule in nature is that there are no rules. Contact: Chris Shaw E-mail: Chris.Shaw@qub.ac.uk 23 http://www.thecolumn.eu.com

Table of Contents for the Digital Edition of The Column - December 2008

The Column - December 2008
Contents
Do Wrinkle Creams Really Work?
News
Incognito
Market Trends and Analysis
Tips and Tricks: GPC/SEC
UHPLC for the Analysis of Paracetamol
Q&A

The Column - December 2008