Saliva test for cancer? Capture new ideas cancer markers
Closely related to the sialylated glycan (the SGs) occurrence, progression and metastasis of various tumors with abnormal expression, and sialylated glycoproteins have been widely used in clinical cancer biomarkers. However, identification and comprehensive analysis of SGs is very complex, urgent need for a new, effective way to capture the SGs from biological samples. Recently, Dalian Institute of Chemical Physics the brainchild of Liang and Yan Qing light team reported a novel dynamic Schiff base hydrolysis of covalent chemical strategies for accurate capture SGs. combined with traditional static affinity and irreversible chemical bonds of different strategies, this study dynamic covalent chemistry strategies, use glucopyranoside – Schiff base-modified silicone established a highly specific and efficient, mild, reversible the SG capture method, then, the researchers detailed story behind the story of the Schiff base hydrolysis, showing the unique advantages of dynamic covalent chemistry sugar proteomics and biomolecular sensing in promoting the sugar proteomics development of sialic acid and sensing means, the development of cancer biomarkers also have a more substantial prospects.
The basic principle is as follows: 1b, 4-formylphenyl -D- glucopyranose and (3-aminopropyl) – imidization glucopyranoside formed between the trimethoxysilane-modified silicone – Schiff base-modified silicone material (Glu-Schiff base @ SiO2). In effect the biological sample SGs Schiff base hydrolysis of precursor amine complex formed and SG- reagent Glu, Glu ordered self-assembly can further facilitate the hydrolysis reaction, to enable efficient enrichment of the biological sample. Under the action of ammonia, and the reverse reaction can be carried out, in order to achieve non-destructive recovery of the sample.
In the conventional mixed solution of acetonitrile and water as eluent glycopeptide elution method completely different from the method to Glu-Schiff base @ SiO2 prepared to feed the micro-column solid phase extraction column (SPE ), containing 1% formic acid (FA) 85% acetonitrile (ACN) / H2O peptide carrier liquid, 80% ACN / H2O containing 1% of the FA washing solution, aqueous ammonia (10% NH3 · H2O) as an eluent . The results show that, Glu-Schiff-base @ SiO2 material model protein human serum samples and exhibited excellent sialylated glycopeptide (the SGP) selective enrichment. SGP and has a high adsorption capacity and recovery, the adsorption capacity is 120mg · g-1, significantly higher than the commercial ZIC-HILIC (10 mg · g-1) and Sepharose (10 mg · g-1), Glu-Schiff base @ SiO2 recoveries of up to 95.5%. This feature is particularly suitable for the capture and analysis of SGPs, so that would help in the sensing sialic acid, sialic acid analysis of the cell surface, tumor cell sorting applications and early diagnosis of various cancers and the like.
Why Glu-Schiff base @ SiO2 material would be enriched SGs have such excellent results so far? To answer this question, the researchers introduces two molecular models, Neu5Ac (SGPs outermost molecules) and 4- (phenylethyl imine) methyl] phenyl -D- pyranoside (Schiff base a) (core component Glu-Schiff base @ SiO2 material). Slow hydrolysis of the Schiff base A PEA and generates 4-formylphenyl β-Dglucopyranoside (B), Schiff base A will accelerate hydrolysis after addition of Neu5Ac, Neu5Ac and there between hydrolyzate and strong interaction to form highly stable PEA-Neu5Ac complex. More interestingly, the researchers found that B has a strong ability to self-assemble in water, which will promote the hydrolysis reaction and promote the reaction complex with PEA hydrolyzate of Neu5Ac, the Glu-Schiff base @ SiO2 materials exhibit superior SGs affinity.
In this article, researchers from materials science point of view, breaking the traditional chemical stability of the material is the prerequisite for the enrichment material design ideas using Glu-Schiff base @ SiO2 material as a \”self-sacrifice\” agents play a role, it reveals the necessity Schiff base hydrolysis reaction, indicating the great potential of dynamic covalent chemistry strategies in capturing target biomolecules. Related research in order to \”What Is Hidden Behind Schiff Base Hydrolysis? Dynamic Covalent Chemistry for the Precise Capture of Sialylated Glycans\” was published in JACS . The full text link: https: //pubs.acs.org/doi/10.1021/jacs.0c01970