Hydrogen peroxide for disulfide bridge formation in methionine-containing peptides

Abstract

Two methionine-containing peptides, endothelin 1 and the 1-16 fragment of the receptor of the plasminogen activator 1 for human urokinase, were synthesized and cyclized by hydrogen peroxide. Endothelin 1 was obtained by using regioselective and random schemes of disulfide bond formation. The conditions of cyclization that provided the target products in high purity were found. The general potential of disulfide bond formation by means of hydrogen peroxide was demonstrated for methionine-containing peptides. The method resulted in target products containing insignificant quantities of the corresponding Met-sulfoxide derivatives.

Increasing the O2 Resistance of the [FeFe]-Hydrogenase CbA5H through Enhanced Protein Flexibility

“…The crystal structure of CbA5H suggests that M382 forms hydrophobic contacts with residues L549 and I552 (Figure B, inset), which might coordinate the peptide chain. Methionine residues often stabilize protein structures by forming hydrophobic interactions with the nearby residues. , The highly flexible side chain with the unique properties of the thioether sulfur render this amino acid as highly versatile. ,− It was proposed that methionines form tighter van der Waals contacts than other hydrophobic side chains, which provide a natural anchor point in the protein environment . The replacement of a methionine can abolish such interactions and therefore may increase the flexibility of peptide chains .…”

“… 49 , 50 The highly flexible side chain with the unique properties of the thioether sulfur render this amino acid as highly versatile. 49 , 51 − 53 It was proposed that methionines form tighter van der Waals contacts than other hydrophobic side chains, which provide a natural anchor point in the protein environment. 54 The replacement of a methionine can abolish such interactions and therefore may increase the flexibility of peptide chains.…”

An Alkyne Rod to Constrain a Peptide Backbone in an Extended Conformation

“…Covalent bonding of the side chains of two amino acids (the side chain‐to‐side chain strategy) to form a peptide macrocycle in a constrained conformation is called peptide stapling , . From the chemical perspective, there are many different approaches used for peptide macrocyclization, the most attractive of which include azide–alkyne click reactions, macrolactamization,, ring‐closing metathesis and disulfide bridge formation , . Here, we describe the use of an alkyne rod constraint attached to the amide nitrogens of a short peptide backbone via one and/or two methylene spacers to lock that peptide backbone in an extended conformation.…”