Resistance proof, folding-inhibitor drugs

TL;DR

This paper proposes a novel drug design approach using peptides that inhibit protein folding, potentially avoiding resistance issues common with conventional active-site inhibitors.

Contribution

It introduces a non-conventional drug model based on peptides that prevent protein folding, offering an alternative to traditional enzyme inhibition methods.

Findings

Peptides can effectively inhibit protein folding.

Inhibition cannot be bypassed by simple mutations.

Potential for resistance-proof drug development.

Abstract

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 non- conventional 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 resistence.