Usefulness of allosteric modulators

There are distinct advantages to producing physiological responses with allosteric ligands:

• First, there is often a 'ceiling' to the effects of an allosteric modulator. As a consequence, allosteric modulators would be generally much safer in overdosage than orthosteric ligands.

• Second, positive allosteric modulators could selectively 'sensitize' tissues where the endogenous agonist exerts its physiological effects. This will result in an increased response for the same concentration of endogenous messenger present.

• Finally, small molecules can effectively inhibit the interaction of large proteins through allosteric mechanisms (e.g. antagonists of metabotropic glutamate receptors) without the need to compete with those large proteins for binding to the orthosteric site.

0 0

Post a comment