Resistance proof, folding-inhibitor drugs

Conventional drugs work, as a rule, by inhibiting the enzymatic activity of specific proteins, capping their active site. In this paper we present a model of nonconventional drug design based on the inhibiting effects small peptides obtained from segments of the protein itself have on the folding ability of the system. Such peptides attach to the newly expressed (unfolded) protein and inhibit its folding, inhibition which cannot be avoided but through mutations which in any case denaturate the enzyme. These peptides, or their mimetic molecules, can be used as effective alternative drugs to those already available, displaying the advantage of not suffering from the upraise of resistance. (C) 2003 American Institute of Physics.