2015
DOI: 10.1002/anie.201502006
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Highly Amino Acid Selective Hydrolysis of Myoglobin at Aspartate Residues as Promoted by Zirconium(IV)‐Substituted Polyoxometalates

Abstract: SDS-PAGE/Edman degradation and HPLC MS/MS showed that zirconium(IV)-substituted Lindqvist-, Keggin-, and Wells-Dawson-type polyoxometalates (POMs) selectively hydrolyze the protein myoglobin at Asp-X peptide bonds under mildly acidic and neutral conditions. This transformation is the first example of highly sequence selective protein hydrolysis by POMs, a novel class of protein-hydrolyzing agents. The selectivity is directed by Asp residues located on the surface of the protein and is further assisted by elect… Show more

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Cited by 101 publications
(158 citation statements)
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“…This approach relies on coordination properties of given metal ions alone (aqua ions) or in coordinatively unsaturated complexes leading to specific interactions with individual amino acid side chains or short sequences. At pH around 5, Asp-Xaa peptide bonds are selectively cleaved by metal ions as was shown for the HEWL and myoglobin hydrolysis by oxomolybdate and Zr(IV)-substituted POM [78,79]. At a lower pH 2.5, Pd(II) and Pt(II) compounds are effective hydrolytic agents specifically toward the second peptide bond upstream or the first bond downstream from the Met or His residue, respectively [47,83,84].…”
Section: Discussionmentioning
confidence: 84%
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“…This approach relies on coordination properties of given metal ions alone (aqua ions) or in coordinatively unsaturated complexes leading to specific interactions with individual amino acid side chains or short sequences. At pH around 5, Asp-Xaa peptide bonds are selectively cleaved by metal ions as was shown for the HEWL and myoglobin hydrolysis by oxomolybdate and Zr(IV)-substituted POM [78,79]. At a lower pH 2.5, Pd(II) and Pt(II) compounds are effective hydrolytic agents specifically toward the second peptide bond upstream or the first bond downstream from the Met or His residue, respectively [47,83,84].…”
Section: Discussionmentioning
confidence: 84%
“…A similar selectivity was not observed for Glu residues. Despite the presence of a carboxyl group capable to bind oxophilic Zr(IV), Glu forms a six-membered intermediate, less stable than the five-membered one with Asp [79].…”
Section: Oxoanions and Pomsmentioning
confidence: 99%
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“…Ce IV and Zr IV substituted POMs were shown to promote selective hydrolysis of a variety of water soluble proteins, ranging from flexible polypeptide such as oxidized insulin chain B (Sap et al, 2015), to larger, globular proteins such as hen egg white lysozyme (Stroobants et al, 2013, 2014d), human serum albumin (HSA) (Goovaerts et al, 2013; Stroobants et al, 2014a,b), horse heart cytochrome c (Cyt c) (Sap et al, 2016) and horse heart myoglobin (Ly et al, 2015a; Ly and Parac-Vogt, 2017). However, the potential of these POMs to act as artificial proteases toward hydrolysis of proteins in the presence of surfactants is still largely unexplored.…”
Section: Introductionmentioning
confidence: 99%
“…Theselective cleavage of proteins and peptides is very useful in protein engineering.A lthough some artificial peptidases (such as uranyl ions, [26] metal-substituted polyoxometalate complexes, [27] MOF-808 [28] )h ave been developed, it is still very challenging to design and synthesize controllable protein-cleaving agents due to the extreme stability of the peptide bond. Theselective cleavage of proteins and peptides is very useful in protein engineering.A lthough some artificial peptidases (such as uranyl ions, [26] metal-substituted polyoxometalate complexes, [27] MOF-808 [28] )h ave been developed, it is still very challenging to design and synthesize controllable protein-cleaving agents due to the extreme stability of the peptide bond.…”
mentioning
confidence: 99%