@article {doi:10.1021/acs.analchem.8b04417,
	title = {Enrichment of Phosphorylated Peptides with Metal{\textendash}Organic Framework Nanosheets for Serum Profiling of Diabetes and Phosphoproteomics Analysis},
	journal = {Analytical Chemistry},
	volume = {90},
	number = {22},
	year = {2018},
	note = {PMID: 30372032},
	pages = {13796-13805},
	abstract = {<p>Capturing phosphopeptides from complicated biological samples is essential for the discovery of new post-translational modification sites and disease diagnostics. Although several two-dimensional (2-D) materials have been used for phosphopeptides capturing, metal\&ndash;organic framework (MOF) nanosheets have not been reported. The Ti-based MOF nanosheets have well-defined 2-D morphology, high density of active sites, large surface area, and an ultrathin structure. Phosphopeptides can be efficiently extracted and superior detection limits of 0.1 fmol μL\&ndash;1 can be achieved even for an extremely low molar ratio of phosphoprotein/nonphosphoprotein (1:10000) mixtures. The selectivity over nonphosphopeptides can be enhanced further by pretreatment with a 10 mM salt solution (β-glycerophosphate disodium, NaCl, or KCl). The performance of 2-D Ti-based MOF nanosheets is much better than Zr-based MOF (Zr-BTB) nanosheets or any other Ti-based 3-D MOF counterpart, such as MIL-125 and NH2-MIL-125. The nanosheets were used for in situ isotope labeling for abnormally regulated phosphopeptides analysis from serum samples of type 2 diabetes patients. The relative quantitative results showed that three of the phosphorylated fibrinogen peptides A (FPA, DpSGEGDFLAEGGGV, DpSGEGDFLAEGGGVR, and ADpSGEGDFLAEGGGVR) were down-regulated, while the other isoform (ADpSGEGDFLAEGGGV) was up-regulated in the serum samples of type 2 diabetes patients compared with those of healthy volunteers. Finally, proteomics analysis showed selective enrichment of phosphopeptides with 2-D Ti-based MOF nanosheets from real samples, including tryptic digests of mouse brain neocortex lysate, mouse spinal cord lysate, and mouse testis lysate, followed by LC-MS/MS analysis. Total numbers of 2601, 3208, and 2866 phosphopeptides were successfully identified from the three samples, respectively. The 2-D Ti-based MOF nanosheets significantly improved sample preparation for mass spectrometric analysis in phosphopeptides and phosphoproteomics research.</p>},
	doi = {10.1021/acs.analchem.8b04417},
	url = {https://doi.org/10.1021/acs.analchem.8b04417},
	author = {Yang, Shi-Shu and Chang, Yu-Jie and Zhang, Hao and Yu, Xizhong and Shang, Wenbin and Chen, Gui-Quan and Chen, DDY and Gu, Zhi-Yuan}
}
