Asymmetric synthesis of artificial peptides
Peptides are molecules formed by chemically chained a-amino acids (HO2CCH(R)-NH2) that regulate most of the biochemical processes that occur in living beings. Today the structures of peptides involved in many diseases are known, but unfortunately most natural peptides cannot be used directly as drugs because they are not able to cross membrane barriers between body organs or because our protease enzymes eliminate them. For this reason, in the last decade, artificial molecules such as peptides, called peptidomimetics, are being studied for the manufacture of new drugs.
The main objectives of the project are:
a) develop the general pathways for the synthesis of ß-peptidomimetic from ß-amino acids (HO2CCH2CH(R)-NH2),
b) analyze their structures and
c) consolidate its biological activity.
The preparation of p -peptidomimetics is also carried out in two ways: a) total asymmetric synthesis and b) stereoselective alkylation of<-lactam.
In line with the first pathway, it has been described above how enantipure amino acids are prepared with raw materials as cheap as camphor and acetylene. This reaction is also widespread and, modifying a reagent used, is also valid for the substitution of ß-amino acids by < -hydroxyacids (HO2CCH2CH(R)-OH).
To treat the second pathway we use<-lactam, i.e. cyclic derivatives of<-amino acids. Peptidomimetics of<-lactam have been first developed in our laboratory and at this time we have just synthesized the b-lactam peptidomimetic of the PLG tripeptide (Prolina-Leuzina-Glycine), which affects the central nervous system.
After the preparation of a series of peptidomimetics, X-ray diffractometry is first analyzed at the ETH Institute in Switzerland and later at the Nuclear Magnetic Resonance Service (NMR) of the Faculty of Chemistry of San Sebastian. These studies allow extracting solid and dissolving peptidomimetic structures and, consequently, determining whether they can interact properly with specific enzymes or receptors. Finally, biochemical tests verify biological activity with enzymes or living beings.
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