Small Cyclic Disulfide Peptides: Synthesis in Preparative Amounts and Characterization by Means of NMR and FT‐IR Spectroscopy

Abstract

Two cyclic disulfide-bridged tetrapeptides [cyclo(Boc−Cys− Pro−Aib−Cys−OMe) and cyclo(Boc−Cys−Pro−Phe−Cys− OMe)] were prepared in high yield and purity. The use of double-walled reaction flasks, which were attached to an external cryostat, gave perfect temperature control of the reaction. The acetamidomethyl and trityl group were used for the protection of the thiol groups of Cys. Disulfide bond formation was obtained by cleavage of the protection groups and subsequent oxidation of the free thiols with iodine under high dilution conditions in one step. The obtained cyclic peptides were checked for purity by analytical HPLC, and identified by NMR spectroscopy and a variety of standard analyt-

Solution and solid state conformational preferences of a family of cyclic disulphide bridged tetrapeptides

“…All reagents and solvents were obtained from different commercial sources and were used without further purification. The preparation of the peptides was carried out following a modified synthetic route introduced for the synthesis of cyclo(Boc‐Cys‐Pro‐ Aib ‐Cys‐OMe) and cyclo(Boc‐Cys‐Pro‐ L‐Phe ‐Cys‐OMe) . Detailed procedures for the synthesis of the new peptides containing L‐ / D‐Ala , L‐ / D‐Trp , and L‐ / D‐Val , and their characterization can be found in the Supporting Information.…”

“…We recently introduced a class of small cyclic tetrapeptides (cf. Figure ), which feature β‐turns, characteristic intramolecular hydrogen bonding, and rigidifying disulphide bonds . The general formula is cyclo(Boc‐Cys‐Pro‐ X ‐Cys‐OMe) with X being either Gly or an L‐ or D‐amino acid.…”

Ultrafast 2D–IR Spectroscopy of Transient Species

“…[45] Due to the stabilizing effect of its disulfide bridge and an intramolecular hydrogen bond, the peptide is very rigid and, according to NMR results, adopts a single b-turn structure in solution. [46] The weak disulfide bond can be cleaved by UV light, providing a molecular photo-trigger, which has been introduced by Hochstrasser and co-workers. [47,48] The FTIR absorption spectrum shows well-resolved bands in the amide I region, which is very sensitive to conformational changes.…”

Two-Dimensional Infrared Spectroscopy of Photoswitchable Peptides

“…Unfortunately, geminate recombination of the liberated thiyl radicals occurred before helix formation could be detected. We have recently used this approach for a much smaller peptide (Figure 4c) (133) that forms a β-turn structure in the disulfide-bridged configuration. Upon photocleavage of the disulfide bridge, the hydrogen bond in the β-turn is destabilized and the ring structure opens.…”