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Title: Hydrolysis of peptides and proteins by metal-substituted polyoxometalate complexes
Other Titles: Hydrolyse van Peptiden en Proteïnen door Metaalgesubstitueerde Polyoxometalaat Complexen
Authors: Ly Thi, Hong Giang
Issue Date: 8-Jun-2015
Abstract: Selective hydrolytic cleavage of the peptide bond in proteins is one of the most important procedures in analytical biochemistry and biotechnology applications. However, this is a challenging task due to the extreme inertness of peptide bond. Commonly used natural proteases are expensive and operate only in a narrow temperature and pH range. They often suffer from self-digestion and often have limited selectivity, making their use in proteomics cumbersome. Therefore, new, efficient, and selective cleaving agents that are sufficiently active at non-denaturing pH and temperature conditions are highly needed. Commonly used natural proteases are expensive and operate only in a narrow temperature and pH range. They often suffer from self-digestion and often have fixed selectivity, making their use in proteomics cumbersome. Therefore, new, efficient, and selective cleaving agents that are sufficiently active under broad pH and temperature conditions are highly needed.
Due to their strong Lewis acidity, several transition metal and lanthanide ions exhibit activity towards peptide bond hydrolysis due to their binding ability to amide carbonyl oxygen atoms, polarizing the peptide bond. However, under mildly acidic and neutral media they often form polynuclear complexes resulting in precipitation which limits their reactivity. Inspired by their reactivity and in order to avoid heterogeneous reaction conditions, we have developed a new way of achieving regioselective cleavage of proteins by combining the enzyme-like molecular recognition ability of a polyoxometalate framework with the hydrolytic activity of strong Lewis acidic transition metal and lanthanide ions, generally referred to as metal-substituted polyoxometalates (MSPs).
In our study, the Lewis acidic metal ions such as ZrIV, CeIV, and TiIV were embedded into tungsten(VI) metal-oxygen framework of Lindqvist, Keggin, and Wels-Dawson types, forming different MSP compounds. These compounds were screened to study the hydrolysis of a dipeptide and the results showed that among three different types of POMs, i.e. Lindqvist, Keggin, and Well-Dawson, the 1:1 Zr(IV)-Lindqvist, 2:2 Zr(IV)-Keggin, and 4:2 Zr(IV)-Wells-Dawson POMs exhibited the highest reactivity within each category of POMs. Therefore, they have been extensively used as catalysts for the hydrolysis of peptide bonds in di-, tri-, tetrapeptides and proteins. In the presence of all these three POMs considerable rate enhancements as compared to the uncatalyzed reactions were obtained and homogeneous peptide bond hydrolysis was achieved for all peptides and protein.
Publication status: published
KU Leuven publication type: TH
Appears in Collections:Molecular Design and Synthesis

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