Tuning the properties of a cyclic RGD-containing tetrapeptide through backbone fluorination.

Stereoselective fluorination is investigated as a method for modulating the properties of a cyclic RGD-containing tetrapeptide. Three key outcomes of fluorination are assessed: (i) the effect on peptide cyclisation efficiency; (ii) the ability to fine-tune the molecular conformation; and (iii) the effect on the cyclic peptides' biological activity. Fluorination is found to exert pronounced effects against all three criteria.

Homologated amino acids with three vicinal fluorines positioned along the backbone: development of a stereoselective synthesis.

Backbone-extended amino acids have a variety of potential applications in peptide and protein science, particularly if the geometry of the amino acid is controllable. Here we describe the synthesis of δ-amino acids that contain three vicinal C-F bonds positioned along the backbone. The ultimately successful synthetic approach emerged through the investigation of several methods based on both electrophilic and nucleophilic fluorination chemistry. We show that different diastereoisomers of this fluorinated δ-amino acid adopt distinct conformations in solution, suggesting that these molecules might have value as shape-controlled building blocks for future applications in peptide science.