FASCICULIN - MODIFICATION OF CARBOXYL GROUPS AND DISCUSSION OF STRUCTURE-ACTIVITY RELATIONSHIP

Norleucine methylester was coupled to carboxylates of fasciculin 2, a snake toxin that inhibits acetylcholinesterase (AChE). This neutralize d negative charges but had no effect on the activity, suggesting that carboxyls do not participate in binding to AChE. Earlier results are d iscussed. Modification of three aromatic amino acids in the peripheral site of AChE, the binding site for fasciculin, decreased tile affinit y 100 to one million times. Neutralizing the charge of cationic groups of fasciculin lowered the affinity only three to seven times, A chang e in either the toxin or enzyme part of a binding site should have abo ut the same effect. Since this was not so, it suggests that cationic g roups of fasciculin do not bind to aromatic rings in the peripheral si te. Copyright (C) 1996 Elsevier Science Ltd