Aza amino acid containing peptides; sythesis optimisation, biological evaluation
Our work is focused on different kinds of peptide family with special tumour accumulation and selectivity (so called tumour homing peptides). One of them is α-MSH peptide family which is the special ligand for the very aggressive melanoma due to their binding of the melanocortin-1 receptor. The structure of the natural α-MSH has been modified in several ways (e.g. substitution of Met→Nle, Phe→D-Phe, or incorporation of D-melphalane, etc.). The other peptide famlily includes the non-small cell lung (NSCL) specific peptides. Unfortunately, the exact mechanism of their action is uncleared, yet. In case of both peptide family the stability, the receptor affinity and/or selectivity of the peptides are key to their effectiveness. Therefore we are looking for the possibilities, especially the new synthetic strategies, which can be applied to enhance their effectivity.
The structure of the biologically active peptides can be significantly influence their effectivity or their mode of action. However some kinds of modification in the sequence (e.g. alteration of the amino acid’s position, Ala-scan, etc) can be easily performed in order to establishe structure-activity relationships, these peptide derivatives have many disadvanteges (e.g. low meatbolic stability, weak receptor selectivity, limited bioavailability, etc.). Circumvent these limitations, the use of peptidomimetics may be ideal tools for identifying peptides properties and their structure-activity relationship. Incorporation of aza amino acid residues in the peptide sequence increases the stability and effectivity of natural peptides. The semicarbazide moiety in the aza-amino acids induces formation of turn secundary structure due to its electrostatic interaction, which is very important for the molecular recognition.
Based on the above mentioned background, combination of our synthetic experiences makes possible to develop a novel synthetic methods toward the synthesis of aza amino acid containing peptidomimetics. These new procedures can result in progression in the field of synthesis of azapeptides.
Ildikó Szabó, Zoltán Bánóczi