Scandium(iii) triflate-promoted serine/threonine-selective peptide bond cleavage

Abstract

The site-selective cleavage of peptide bonds is an important chemical modification that is useful not only for the structural determination of peptides, but also as an artificial modulator of peptide/protein function and properties. Here we report site-selective hydrolysis of peptide bonds at the Ser and Thr positions with a high conversion yield. This chemical cleavage relies on Sc(iii)-promoted N,O-acyl rearrangement and subsequent hydrolysis. The method is applicable to a broad scope of polypeptides with various functional groups, including a post-translationally modified peptide that is unsuitable for enzymatic hydrolysis. The system was further extended to site-selective cleavage of a native protein, Aβ1-42, which is closely related to the onset of Alzheimer's disease.

Synergistic activity of cosecreted natural products from amoebae-associated bacteria

“…The presence of multiple D-and L-alanines, however, rendered its structure elucidation difficult. A recent study showed that scandium(III) triflate promotes selective cleavage of a peptide adjacent to a serine or threonine residue by means of an N,O-acyl rearrangement (34). This was the key to fragment jessenipeptin, which tremendously facilitated subsequent structure elucidation.…”

“…A recent publication by Ni et al (34) describes a scandium(III) triflate-mediated peptide hydrolysis method, which displays selectivity for cleavage of amide bonds adjacent to serine or threonine residues. Hence, we were able to obtain fragment F1, which was purified by HPLC.…”

Amide Bond Activation of Biological Molecules

“…This chemical cleavage relies on Sthe c triflate mediated N to O acyl rearrangement followed by the subsequent hydrolysis of the ester by heating it at 80–100 °C ( Figure 35 ). Complete hydrolysis took place in 18–20 h. The authors have used this approach for the cleavage of various peptides including posttranslationally modified (PTM) peptides and the cleavage of native protein Aβ1-42, which is closely related to Alzheimer’s disease [ 114 ].…”

Molecular fusion of surfactant and Lewis-acid properties for attacking dirt by catalytic bond cleavage

“…confirms a strong coordination of the different Lewis-acidic metal ions. Sc 3+ was selected, because Kanai et al have presented a study in 2017 about triflate salts used for peptide bond-cleavage 19 . However, the authors have not used amphiphilic compounds nor demonstrated stability of the catalysts at elevated pH values in aqueous medium.…”