Impact of β-perfluoroalkyl substitution of proline on the proteolytic stability of its peptide derivatives.

A series of all stereoisomers of β-CF or β-CF substituted prolines and their dipeptide derivatives were synthesized. Mouse plasma stability assay was carried out to study the impact of fluoroalkyl substituents on the proteolytic stability of proline-derived peptides. The effect of the ()-/()-configuration at the C-2 atom in combination with electronic and steric effects imposed by fluoroalkyl groups was addressed to rationalize the difference in the half-life stability of diastereomeric β-CF-Pro-Gly and β-CF-Pro-Gly derivatives and compared to those of parent ()-Pro-Gly and ()-Pro-Gly dipeptides.

A conformationally restricted GABA analogue based on octahydro-1H-cyclopenta[b]pyridine scaffold.

An approach to rel-(4aS,6R,7aR)-octahydro-1H-cyclopenta[b]pyridine-6-carboxylic acid-a bicyclic conformationally restricted γ-aminobutyric acid (GABA) analogue was developed. The eight-step sequence relied on the reaction of 2,3-bis(chloromethyl)pyridine and a C-binucleophile and the catalytic reduction of the pyridine ring as the key steps and allowed for the preparation of the title compound in 9.0% overall yield.

Conformational behaviour of peptides containing a 2-pyrrolidinemethanesulfonic acid (2PyMS) residue.

The conformational behaviour of model peptides containing a 2-pyrrolidinemethanesulfonic acid (2PyMS) residue was studied in both the crystalline state and in solution using X-ray, NMR and IR experiments. It was found that in crystals dipeptide PhC(O)-2PyMS-Phe-NHiPr adopted β-turn conformation, which was not stabilized by an intramolecular hydrogen bond and could be classified as a type IV β-turn. In the crystalline state tripeptide PhC(O)-Ala-2PyMS-Phe-NHiPr existed as an α-turn with uncommon cis-conformation of the amide bond formed by the pyrrolidine nitrogen atom of the 2PyMS residue, for which no close analogue can be envisaged among the tight turns identified so far.