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The incorporation of dehydroamino acid or fragments of oxazole into peptide chain is accompanied by a distorted three-dimensional structure and additionally enables the introduction of non-typical side-chain substituents. Thus, such compounds could be building blocks for obtaining novel foldamers and/or artificial enzymes (artzymes). In this paper, effective synthetic procedures leading to such building blocks—tetrapeptides containing glycyldehydroalanine, glycyldehydrophenylalanine, and glycyloxazole subunits—are described. Peptides containing serine were used as substrates for their conversion into peptides containing dehydroalanine and aminomethyloxazole-4-carboxylic acid while considering possible requirements for the introduction of these fragments into long-chain peptides at the last steps of synthesis.

Background: Dehydropeptides are analogs of peptides containing at least one conjugate double bond between α,β-carbon atoms. Its presence provides unique structural properties and reaction centre for chemical modification. In this study, the series of new class of dipeptides containing S-substituted dehydrocysteine with variety of heterocyclic moieties was prepared. The compounds were designed as the building blocks for the construction of artificial metalloenzymes (artzymes). Therefore, the complexing properties of representative compounds were also evaluated. Furthermore, the acknowledged biological activity of natural dehydropeptides was the reason to extend the study for antiproliferative action of against several cancer cell lines. Methods: The synthetic strategy involves glycyl and phenylalanyl-(Z)-β-bromodehydroalanine as a substrate in one pot addition/elimination reaction of thiols. After deprotection of N-terminal amino group the compounds with triazole ring were tested as complexones for copper(II) ions using potentiometric titration and spectroscopic techniques (UV-Vis, CD, EPR). Finally, the antiproliferative activity was evaluated by sulforhodamine B assay. Results and Conclusions: A simple and efficient procedure for preparation of dipeptides containing S-substituded dehydrocysteine was provided. The peptides containing triazole appeared to be strong complexones of copper(II) ions. Some of the peptides exhibited promising antiproliferative activities against number of cancer cell lines, including cell lines resistant to widely used anticancer agent.

In the title compound, the dehydrodipeptide (Boc–Phe–ΔAla–OiPr, C20H28N2O5), the molecule has a trans conformation of the N-methylamide group. The geometry of the dehydroalanine moiety is to some extent different from those usually found in simple peptides, indicating conjugation between the H2C=C group and the peptide bond. The bond angles around dehydroalanine have unusually high values due to the steric hindrance, the same interaction influencing the slight distortion from planarity of the dehydroalanine. The molecule is stabilized by intramolecular interactions between the isopropyl group and the N atoms of the peptide main chain. In the crystal, an N—H...O hydrogen bond links the molecules into ribbons, giving a herringbone head-to-head packing arrangement extending along the [100] direction. In the stacks, the molecules are linked by weak C—H...O hydrogen-bonding associations.

The title compound, C11H17BrN2O5, is a dehydroamino acid with a C=C bond between the α- and β-C atoms. The amino acid residues are linked trans to each other and there are no strong intramolecular hydrogen bonds. The torsion angles indicate a non-helical conformation of the molecule. The dipeptide folding is influenced by an intermolecular N—H...O hydrogen bond and also minimizes steric repulsion. In the crystal, molecules are linked by strong N—H...O hydrogen bonds, generating (001) sheets. The sheets are linked by weak C—H...O and C—H...Br bonds and short Br...Br [3.4149 (3) Å] interactions.