Download Peptidomimetics- A definition

Peptidomimetics- A definition
• Compounds derived from peptides and proteins and
obtained by structural modification using unnatural
amino acids, conformational restraints.
• Peptidomimetic drugs bridge the gap between simple
peptides and the nonpeptide synthetic structures, in
delineating pharmacophores, and in helping to
translate peptides into small nonpeptide compounds
• In its broadest sense, peptidomimetics is sometimes
used to designate organic molecules mimicking some
properties of peptide ligands.
Molecular mimicry is an activity of central importance in drug
research. Very often, the drugs that are created are conceived as
mimics of substances known to interact with the biological system
considered (hormones, peptides and transmitters).
Peptidomimetic molecules are regular organic molecules which are
conceived to mimic the structure of an endogenous peptide. These
peptidomimetics are valuable because peptides can rarely be
developed as drugs. In general peptides are:
•Biologically unstable
•Poorly absorbed
•Rapidly metabolised
A non-peptide molecule enables overcoming of these shortcomings.
These synthetic molecules allow these peptidomimetic drugs to be
optimised for :
•Specificity
•Oral bioavailability
•Pharmacokinetic properties
Example:
Lam and co-workers succeeded in 1994 to develop potent non-peptide
inhibitors of HIV protease starting from a molecule identified from the
Cambridge Structural Database in terms of distance among 2
hydrophobic groups and a hydroxyl group found in the crystal
structure of the protein-peptidyl ligand complex. They chose the
starting molecule among many hits based on the conformity and Hbonding potential to the receptor cavity without making any other
assumptions.
Lam, P.Y.S., Ladhav, P.K., Eyermann, C.J., Hodge, C.N., Ru, Y., Bacheler, L.T.,
Meek, T.L., Otto, M.J., Rayner, M.M., Wong, Y.N., Chang, C.H., Weber, P.C., Jackson,
D.A., Sharpe, T.R., and Erickson-Viitanen, S., (1994). Rational design of potent,
bioavailable, nonpeptide cyclic ureas as HIV protease inhibitors. Science , 263,
380-384.