CONSTRAINED BETA-AMINO ACIDS AS MOLECULAR TOOLS FOR THE PREPARATION OF FOLDAMERS

In these three years, as PhD student, I was involved in different projects regarding the synthesis of new enantiopure beta-amino acids, their use for the preparation of small alpha/beta-peptide sequences and the study of their secondary structure. All hybrid alpha/beta-peptides were studied using NMR Spectroscopy (1H, 13C, HMBC, HMQC, NOESY; ROESY). Molecular modelling was also performed in collaboration with Prof. Contini, from DISFARM, Università degli Studi di Milano. In the first part of my thesis I reported on the synthesis of: - tetrahydroisoquinoline 4-carboxylic acid and its use in the preparation of alpha/beta-peptides. This new beta-amino acid, coupled with beta-Ala, can stabilize a flexible reverse turn conformation, depending on its stereochemistry; - beta-Morpholino-amino acid. This new beta-amino acid, prepared in enantiopure form, stabilizes a reverse gamma-turn conformation when inserted in alpha/beta-peptides; - beta2,3-diaryl-amino acids and preparation of alpha/beta-peptides. The secondary structure of each peptide was studied. Moreover, self-assembly of a ααβ-tripeptide composed by the beta2,3-diaryl amino acid coupled with L-Ala-L-Arg was investigated. In the second part of this thesis I focused on two other subjects beyond the beta-amino acids, that are: - the synthesis of isoxazoline containing scaffold. Also in this case, model peptides were prepared and their secondary structure were studied; it was found that our scaffold induce a turn able to stabilize a beta-hairpin. - the synthesis and study on Double Functionalized Collagen Model Peptides. This part of my thesis was performed during my internship at ETH (Eidgenössische Technische Hochschule, Zürich, Switzerland) in Wennemers Group.