Peptidomimetics

Peptidomimetics

Many research groups, both in academia and in pharmaceutical companies search constantly for non-peptide compounds that have better bioavailability and stability, perhaps even with greater receptor selectivity. The known structure-activity interactions and conformational foldings of peptide structures aid a great deal in the design of novel peptidomimetics.

Peptidomimetics

Peptidomimetics are compounds specially derived from peptides and protein by structural modifications using unnatural amino acids and conformational restraints. Peptides are becoming extremely popular with researchers because they affect such a wide range of cellular activity. Once a peptide crosses the cell membrane, it often loses stability. Peptidomimetics, however, may be the answer. There are several different ways that organic chemists can alter and modify the peptides. The modifications involve changes to the peptide that do not occur naturally, such as incorporating unnatural amino acids, replacing the peptide bond, and altering backbones.

Peptide Design

There are a number of factors that help in the rational design of PM’s such us: binding site optimal fit, conformational stabilization, (given by rigid elements and the positioning of specific functional groups), polar or hydrophobic regions (inside strategic reactive pockets) that favor the basic atomic interactions provided by hydrogen , electrostatic and hydrophobic bonding.

Natural Peptide

There are many instances where the native information within a natural peptide ligand can be conferred/duplicated or mimetized into a non-peptide molecule, preferably of low molecular weight, hence the basis for the field of peptidomimetics(PM’s). The desire to convey the three dimensional information present in a peptide into small nonpeptide molecules is what encompasses the field of peptidomimetics.

Peptide Mimetics

The goal in PM’s is to obtain molecules that mimic the specific molecular interactions of natural proteins and their ligands. The protein to protein interaction of biologivally active peptides at the receptor level can be obtained by small molecules, in an agonistic fashion or can be blocked, in an antagonistic fashion.