Peptidomimetics

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.

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. 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.

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.

To obtain PM's generally the biological researcher will have to screen compound libraries(either natural products or synthetic products). Combinatorial chemistry, amethod that was heavily used in the mid to late 90's can be a tool to generate vast numbers of peptidic and non-peptidic molecules As an example of a PM's , an inhibitor of angiotensin-converting enzyme (ACE), was developed, this PM's is called Captopril. Also, morphine , an opiod alkaloid, represents a classic example of a nonpeptidic compound found that mimics an endogenous peptide. Morphine replicates the biological effect of beta endorphin, on the respective receptor. A number of important aspects regarding conformational resctriction, peptide bond replacement, addition of turn mimetics and combinatorial library screening ,are investigated in order to search and find novel ligands, within the field of peptidomimetics.

Peptidomimetics

By: Bio-Synthesis Inc.

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