Abstract
In this work, we developed an efficient “molecularly imprinted polymer microzymes and inorganic magnetic nanozymes” synergistic catalysis strategy for the formation of disulfide bonds in peptides. The polymeric microzymes showed excellent selectivity toward the template peptide as well as the main reactant (linear peptide), and the Fe3O4 magnetic nanoparticle (MNP) nanozymes inhibited the intermolecular reaction during the formation of disulfide bonds in peptides. As a result, the integration of the two different artificial enzymes in one process facilitates the intramolecular cyclization in high product yields (59.3%) with excellent selectivity. Mechanism study indicates the synergistic effect was occurred by using a “reversed solid phase synthesis” strategy with an enhanced shift of reaction balance to product generation. We believe the synergistic catalysis by “polymeric microzymes and inorganic nanozymes” presented in the present work may open new opportunities in creation of multifunctional enzyme mimics for sensing, imaging, and drug delivery.
Highlights
As a growth hormone inhibiting hormone, tetradecapeptide somatostatin (SST) was widely found in body organs of animals
Precipitation polymerization with a programmed initiator change strategy was an efficient way for synthesis of molecularly imprinted polymer (MIP) MGs (Meng et al, 2009)
Utilizing scanning electron microscope (SEM) and dynamic light scattering (DLS) measurements, our previous work has shown that the MIP MGs owned a dry diameter of ∼100 nm and a wet diameter of ∼280 nm, respectively
Summary
As a growth hormone inhibiting hormone, tetradecapeptide somatostatin (SST) was widely found in body organs of animals (e.g., the brain tissue, gastrointestinal, and pancreatic; Brazeau et al, 1974). SST with disulfide bridges is usually synthesized via liquid-phase method or solid-phase method (Martín-Gago et al, 2014). In both methods, the final step is intramolecular cyclization of peptides between the two strategically selected cysteine residues (Cys). The general methods for this final step (the oxidation of Cys into disulfide bridges) suffered the following problem: the linear peptides were to form byproducts such as dimerization or oligomerization. To control the oxidation process and to obtain the desirable products, decreasing the concentration of linear peptide and adjusting the oxidization condition have been the main methods to currently improve the yield of the cyclization of peptides (Cheneval et al, 2014)
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