Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Nuclear magnetic resonance spectroscopy of proteins wikipedia , lookup
Implicit solvation wikipedia , lookup
List of types of proteins wikipedia , lookup
Protein mass spectrometry wikipedia , lookup
Circular dichroism wikipedia , lookup
Degradomics wikipedia , lookup
Ribosomally synthesized and post-translationally modified peptides wikipedia , lookup
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.