Differentiation and Relative Quantitation of Disaccharide Iso-mers by

Subscriber access provided by ECU Libraries

Technical Note

Differentiation and Relative Quantitation of Disaccharide Iso-mers by MALDI-TOF/TOF Mass Spectrometry Lingpeng Zhan, Xiaobo Xie, Yafeng Li, Huihui Liu, Caiqiao Xiong, and Zongxiu Nie Anal. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.analchem.7b03735 • Publication Date (Web): 12 Jan 2018 Downloaded from http://pubs.acs.org on January 12, 2018

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

Analytical Chemistry is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 7 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Analytical Chemistry

Differentiation and Relative Quantitation of Disaccharide Isomers by MALDI-TOF/TOF Mass Spectrometry Ling-Peng Zhan†‡, Xiaobo Xie†‡, Yafeng Li†, Huihui Liu†, Caiqiao Xiong†, and Zongxiu Nie*†‡§ †Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China ‡University of Chinese Academy of Sciences, Beijing 100049, China §National Center for Mass Spectrometry in Beijing, Beijing 100190, China ABSTRACT: Saccharide isomer differentiation has been a challenge in glycomics, as the lack of technology to decipher fully the diverse structures of compositions, linkages and anomeric configurations. Several mass spectrometry-based methods have been applied to the discrimination of disaccharide isomers, but limited quantitative analyses have been reported. In the present study, MALDI-LIFT-TOF/TOF has been investigated to differentiate and relatively quantify underivatized glucose-containing disaccharide isomers that differ in composition, connectivity or configuration. N-(1-naphthyl)ethylenediamine dihydrochloride (NEDC) was used as a highly sensitive matrix without matrix interferences in low mass range, thus yielding intense chloride-attached disaccharide ions [M+Cl]- , which could be fragmented to give diagnostic characteristic fragment patterns for distinguishing these isomers. Three different types of disaccharide isomers were successfully relatively quantified in a binary mixture using the specific product ion pairs. Finally, this method was utilized to identify and relatively quantify two disaccharide isomers in Medicago leaf (maltose and sucrose) without numerous preparation steps. In general, this method is a fast, effective, and robust method for rapid differentiation and quantitation of disaccharide isomers in complex medium.

Though carbohydrates are important for understanding biological system, glycomics has lagged behind the development of genomics and proteomics, due to inherent diversity of the constituent monosaccharides, glycosidic linkages, and anomeric configurations. Mass spectrometry (MS) has become an indispensable tool in characterizing glycan structure with the advantages of low sample consumption, high speed and high sensitivity. Several MS-based methods have been developed to differentiate glycan isomers, which can be divided into two main strategies: tandem mass spectrometry (MS/MS) and ion mobility mass spectrometry (IM-MS). Tandem mass spectrometry has been widely used in glycan structure analysis and isomer distinction for a long time, such as collision-induced dissociation (CID)1,2, negative electron transfer dissociation (NETD)3, electron detachment dissociation (EDD)4 and ultraviolet photodissociation (UVPD)5,6. Base on the drift times and collisional cross sections measured by IM-MS, some glycan isomers can be distinguishing from each other7-11. However, the direct separation and differentiation of underivatized disaccharide isomers by IM-MS seems to be very difficult10. In contrast, MS/MS-based strategies have been developed to distinguish underivatized disaccharide isomers in both positive12-16 and negative modes17-20. To improve the differentiation of isomers in positive mode, metal-adducts or noncovalent complexes formed with disaccharides were fragmented instead of their protonation forms. In comparison with tandem MS in the positive mode, the discrimination of disaccharide isomers was more readily achieved by comparing fragmentation pattern of deprotonated ions [M-H]-, which yields abundant cross-ring cleavage products. For example, a characteristic anion m/z 221 is frequently observed upon [M-H]- dis-

sociated by low energy CID, which can be further fragmented to yield specific fragment pattern for the determination of the stereochemistries and anomeric configurations of the nonreducing monosaccharide units21-23. This has been attributed to that deprotonation sites of glycan are highly mobile24,25, resulting in more fragments. However，the formation of deprotonated ions is not so much easy as its sodiated counterparts. Therefore, various anions have been explored to form anionic adducts of neutral glycans to improve the detection sensitivity, such as chloride18. The anion adducts would lose [H+anion] to form [M-H]- in the process of tandem MS, which decompose subsequently to yield cross-ring cleavage fragments. The different ratios of Cl-/non-Cl- products and consecutive fragmentation of the chloride-adduct disaccharides, have been reported for the differentiation of anomeric isomers26. Moreover, more efficient cross-ring cleavage can be achieved by high energy collision induced dissociation rather than low-energy CID27. Although numerous MS-based strategies have been proposed to differentiate carbohydrate isomers, the quantification of glycan isomers was rarely reported. The reported quantification applications are generally based on the following methods: (1) MS signal comparison of isotopic or mass tag labeling standard28; (2) direct intensity evaluation based on the chromatography or ion mobility9; (3) specific fragment in tandem MS, such as kinetic method29-31. The labeling method was not practical for saccharide isomers in the same sample, because of that the labeling reaction is not isomer-specific. Although IMMS have been reported to achieve successful separation and identification of nine PMP-derivatized disaccharide isomers, the quantification was hindered by the low mobility resolution that is insufficient to achieve baseline separation of distinct

ACS Paragon Plus Environment

Analytical Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

glycan isomers. The concept of kinetic method was first proposed to quantify enantiomeric small peptide32. This method was later implemented to quantitative analysis of monosaccharides29,30 and disaccharide isomers31, but it was complicated. A recent report utilized similar strategy to quantify the monosaccharide isomer33. The complexes formed with cucurbit[7]uril (CB[7]) and monosaccharide isomers yielded distinct fragmentation patterns upon collisional activation, which were used to quantify the monosaccharide isomers successfully. MALDI tandem mass spectrometry as a high throughput, high speed and sensitive method, has been widely used in structural analysis and quantitation of glycans. For example, MALDI in source decay (ISD) has been applied to distinguish and relatively quantify the glycan isomers based on the specific fragments34. However, ISD requires ultra-pure sample, not suitable for complex mixture. Moreover, MALDI-TOF/TOF has also been reported as a powerful method for quantifying carbohydrate isomers35,36, but common MALDI matrix used in the analyses of glycans will produce abundant peaks in the low mass range (m/z 3) of m/z 161 to 179 in comparison with that of the βconfiguration laminaribiose(Glcβ1-3Glc). Additionally, in the case of compositional isomers studied here, such as lactose (Galβ1-4Glc) versus cellobiose (Glcβ1-4Glc) or melibiose (Galα1-6Glc) versus isomaltose (Glcα1-6Glc), the differentiation can also be achieved, as shown in Fig.1a, 1c, 1e and 1f. Specifically, the obvious difference in


Page 3 of 7 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Figure 1. The MALDI-TOF/TOF spectra of the precusor ions [M+Cl]- (m/z 377) obtained from nine disaccharides. The nine disaccharide isomers were marked as circled number 1-9. the ratio of m/z 263 to 281 can be applied to distinguish cellovoltage. It was different from CID, however the fragments of biose and lactose. The two isomers, isomaltose and melibiose, disaccharide were similar with ESI-CID26. We also obtained yielded nearly identical fragmentation patterns, however, the the low energy CID spectra with MALDI-Q-FTICR (Fig.S3), slight difference of the calculated ratios of m/z 251:281 and which showed similar fragmentation pattern to the TOF/TOF 281:179 can also be used for the discrimination of these two spectra. However, it was found that cross-ring fragments in isomers, as shown in Fig.S1. CID spectra were relatively lower than those in LIFT spectra, especially in the case of maltose and isomaltose (Fig.S3 b and The fragmentation profiles by LIFT and post-source decay e). (PSD)19 can be seen to be somewhat different in the relative intensities of characteristic product ions, although the major Relative Quantification of Disaccharide Isomers in Differneutral losses obtained through the two technologies have ent Types The quantitative analysis of mixed disaccharide isomers was shown a certain degree of similarity. In the case of gentiobiose, much more difficult than their structural identification. For the the intensity of ion m/z 221 was lower than that of m/z 281 in methods based on ESI-MS/MS, competing binding as well as the LIFT spectrum, as shown in Fig.1d, but the relative ratio in ionization must be considered while quantifying the sacchathe PSD spectrum was in reverse. As PSD spectrum recorded ride isomer in the mixtures29. Moreover, other molecules like from several segments, relative intensity of fragments in different segments was not reproducible as MALDI ionization amino acids14 in the complex medium would form complexes 20 condition and the intensity of precursor ions varies . The with glycans, affecting the quantitative analysis. To expand MALDI-TOF/TOF applications in the relative quantitative LIFT technology acquiring the TOF/TOF spectrum in one analysis of a specific isomer in their mixture, three sets of event has been developed to overcome these drawbacks39,40, glycan isomers that differ in composition, connectivity and which is compatible to subsequent quantitative analysis. Simiconfiguration, were used, including composition isomers with lar to the PSD, the relative peak intensity of two fragments cellobiose (Glcβ1-4Glc) and lactose (Galβ1-4Glc), connectivistudied here is fairly stable regardless of laser intensity (Fig ty isomers with isomaltose (Glcα1-6Glc) and maltose (Glcα1S2), which is important for quantification analysis. 4Glc), configuration anomers with gentiobiose (Glcβ1-6Glc) The TOF/TOF dissociation involves decomposition of metand isomaltose (Glcα1-6Glc), respectively. To build the caliastable analyte ions, which absorbing high energies by collibration curve, we prepare seven mock mixtures with identical sion excitation with the matrix ion after laser activation. The collision energy was high due to applied high acceleration



total molars of disaccharides but variable ratios of two isomers at 10:1, 5:1, 2:1, 1:1, 1:2, 1:5 and 1:10, respectively. The LIFT spectrum of mixed isomers can be decomposed into a linear combination of LIFT spectra of individual isomers. The calibration curve was built using the method as described elsewhere33. Briefly, R R α R α

(1) where Rmix, RA, RB represent the intensity ratios of two specific fragments from isomer mixture, isomer A and isomer B, respectively. The αA and αB are fractions of A and B in the gas phase. The values of R can be obtained directly from the LIFT spectra. The equation can be converted into (2)

Page 4 of 7

This method was further applied to quantitative analyses of the connectivity isomers. A pair of linkage isomers, isomaltose and maltose with respective linkage positions 1-6 and 1-4 (Fig.3a), were chosen as the models. An obvious difference in the fragmentation patterns was observed between these two linkage-isomers, as shown in Fig.1b and e. As shown in Fig.3b, the relative abundances of the fragments at m/z 161 changed along with the molar ratio of these two isomers. Thus, the ions at m/z 161 and 179 were finally chosen for relative quantitation of the two isomers. The results showed an excellent linearity, as R2 was about 0.99. The linkage-isomers generally produced obviously distinct fragment patterns, thus different type of ions can be used for quantitative analyses.

And the relationship between α and c can be viewed as

n

(3)

where the c values represent their concentrations in solution. The ratios of isomers in the gas phase are not directly comparable to that in solution, due to the different efficiencies of ionization and fragmentation. The ratio of αA to αB are calculated from the intensity ratios R of selected product ions, while the ratio of cA to cB are known. Then we construct the calibration curve by plotting the ratio of α values against that of c values. The compositional isomer examples used here were cellobiose and lactose with different first monosaccharide unit corresponding to glucose and galactose, which differed only in the orientation of one hydroxyl group at the fourth carbon (Fig.2a). Such a subtle structural difference generally resulted in non-separation of these two disaccharides even by high resolution ion mobility9. The MS/MS spectra of these two isomers were different in the ratio of specific fragments m/z 263 to 281, as clearly shown in Fig.2b. The fragment ion m/z 281 was decreasing as the fraction of lactose in mixtures increase gradually. Hence, the calibration curve can be plotted by the ratio of fractions α of cellobiose to lactose in the gas phase versus the molar ratio of cellobiose to lactose in these mixtures. As showed in Figure 2c, the curve in the given dynamic response range showed a good linearity for the two compositional isomers (R2=0.988).

Figure 2. Calibration curve of compositional isomers, lactose and cellobiose, constructed with fragment ions m/z 263 and 281. (a) the structures of lactose and cellobiose; (b) the diagnostic product ion pair used to construct the calibration curve, m/z 263 and 281, in various mixtures with different ratio of disaccharides isomers (molar ratios of cellobiose and lactose were 1:0, 5:1, 1:5, 0:1); (c) The calibration curve.

Figure 3. Calibration curve of linkage isomers, isomaltose and maltose, using the product ion pair m/z 161 and 179. a) Structures of maltose and isomaltose; b) The characteristic fragment used to build the curve, m/z 161 and 179 in various mixtures; c) the calibration curve. Additionally, the capacity of this method for relatively quantifying α- and β-configuration anomers was evaluated by using gentiobiose (Glcβ1-6Glc) and isomaltose (Glcα1-6Glc) as example. The configurational control is a challenge during glycan chemical synthesis9, thus the differentiation and quantification analyses are of great importance. The two disaccharides are stereoisomers only differing in the stereochemistry of the connectivity of two 1-6 linked Glc molecules (Fig.4a). The relative abundance of the ions m/z 281 to m/z 251 increased with the increasing fraction of isomaltose in mixtures, as shown in Fig.4b. The ratio of m/z 281 to 251 was selected to calculate the ratio of α values. The result showed that the configurational isomer was quantified successfully (Fig.4c). From the relationship of gas phase ratio and solution ratio of the studied disaccharide isomers, we observed the different efficiencies of detection and fragmentation (Discussed in Supporting Information). We compared the limit of detection of these isomers and determine that how low fraction of one low abundance isomer would be detectable in the mixture. We found that the linear relationship can hold even in the mixture with high ratios (i.e. higher than 10 or lower than 0.1) of two isomers (Fig.S4), which depend on the efficiencies of detection and fragmentation, and the selected fragments. Moreover, this method has also been applied to discrimination and relative quantitation of trisaccharide isomers. For example, the LIFT spectra of isomaltotriose and maltotriose, as shown in Fig S5a and 5e, respectively, were different. Specifically, the product ions m/z 161 and 425 have been observed in the spectrum of maltotriose while absent in that of isomaltotriose. In the analyses of mixtures of these two isomers, the abundances of fragments m/z 161 and 425 decreased gradually


4

Page 5 of 7 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Analytical Chemistry with the decreasing content of maltotriose. The calibration curve constructed from fragments m/z 161 and 383 showed great linearity, as shown in Fig S6.

Figure 4. Calibration curve for quantification of configurational anomers, gentiobiose and isomaltose, using the fragment pair m/z 251 and 281. a) Structures of gentiobiose and isomaltose. b) The characteristic fragment used to build the curve, m/z 251 and 281, in various mixtures. c) The calibration curve. Relative Quantification of Disaccharide Isomers in Plants Disaccharides are ubiquitous in various biological samples, such as plants, honey and milk. The detection of disaccharides in real sample is quite difficult, due to low ionization efficiencies and complex matrix interferences. As a proof of concept, structural identification and relative quantitation of two disaccharide isomers in Medicago leaf with minimal pretreatment have been achieved using MALDI-TOF/TOF. The disaccharides in the extract of Medicago leaf was detected as [M+Cl]- adducts, i.e. m/z 377 (Fig.S7). After dissociation in the flight tube, product ions at m/z 161, 179, 197, 215, 221, 263, 281 and 341 were obtained, as shown in Fig.5a and b. The characteristic fragments at m/z 215 as well as the extremely intense peak at m/z 341 were assigned as diagnostic ions of sucrose, as shown in Fig.1i. The minor fragments of sucrose at lower mass range reduced the difficulty for the identification of other disaccharides. According to the principle summarized in Table 1, the absence of m/z 251 and the ratio of m/z 263 and 281 were mainly attributed to fragmentation feature of maltose. Because the fraction of maltose in the mixture was very low, we built the calibration curve with ten mock mixtures (mentioned in the experimental section). Following the similar quantitative method, the fragments m/z 281 and 341 (Fig.S8) were selected to build the calibration curve (Fig.5c). The ratio of c[maltose] to c[sucrose] in the extracted Medicago leaf sample was calculated as 0.06. It can be concluded that Medicago leaf extract contains a lot of sucrose but only a little maltose. Moreover, the LIFT spectrum (Fig.S9) of m/z 377 in the extract of the Medicago stem indicated that fewer level of maltose exists in the stem than in the leaf, only two percent compared with sucrose.

Figure 5. Relative quantification of disaccharides in Medicago leaves. (a) Full LIFT mass spectrum of disaccharide extracted from Medicago leaves; (b) enlarged LIFT mass spectrum of (a); (c) calibration curve of sucrose and maltose. Conclusions An efficient but robust MALDI-LIFT-TOF/TOF is developed to rapidly distinguish disaccharide isomers as well as relatively quantify them in a binary mixture based on their characteristic fragment patterns. Structural elucidation and relative quantitation of disaccharide isomers that differ in composition, connectivity or configuration were achieved. Due to its highly sensitivity and matrix tolerance, this method has been successfully applied to confirm two disaccharide isomers and determine the relative ratio of maltose to sucrose in the leaves of Medicago. This method can be further applied to determine the amounts of a specific disaccharide in complex sample based on standard addition method, in which another disaccharide with distinct fragment pattern should be added instead of the use of expensive isotopic labeling standard, for example the disaccharide uptake by microorganism41,42. Additionally, the combination of our method and MALDI-MS imaging can be used to depict disaccharide isomers distribution in complex biological sample.

ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website.


5


Supplementary ﬁgures (PDF)

AUTHOR INFORMATION Corresponding Author * E-mail: [email protected]

Notes

The authors declare no competing financial interest. ACKNOWLEDGMENT

This work was supported by grants from the National Natural Sciences Foundation of China (Grant Nos. 21625504, 21505140, 21621062, 21475139, 21675160 and 21790390/21790392), and Chinese Academy of Sciences.

REFERENCES (1) Domon, B.; Costello, C. E. Glycoconjugate Journal 1988, 5, 397-409. (2) Ashline, D. J.; Lapadula, A. J.; Liu, Y.-H.; Lin, M.; Grace, M.; Pramanik, B.; Reinhold, V. N. Analytical chemistry 2007, 79, 3830-3842. (3) Wolff, J. J.; Leach, F. E.; Laremore, T. N.; Kaplan, D. A.; Easterling, M. L.; Linhardt, R. J.; Amster, I. J. Analytical chemistry 2010, 82, 3460-3466. (4) Agyekum, I.; Zong, C.; Boons, G.-J.; Amster, I. J. Journal of the American Society for Mass Spectrometry 2017, 28, 1741-1750. (5) Lee, S.; Valentine, S. J.; Reilly, J. P.; Clemmer, D. E. International Journal of Mass Spectrometry 2012, 309, 161-167. (6) Devakumar, A.; Mechref, Y.; Kang, P.; Novotny, M.; Reilly, J. Journal of the American Society for Mass Spectrometry 2008, 19, 1027-1040. (7) Hoffmann, W.; Hofmann, J.; Pagel, K. Journal of the American Society for Mass Spectrometry 2014, 25, 471-479. (8) Both, P.; Green, A. P.; Gray, C. J.; Šardzík, R.; Voglmeir, J.; Fontana, C.; Austeri, M.; Rejzek, M.; Richardson, D.; Field, R. A.; Widmalm, G.; Flitsch, S. L.; Eyers, C. E. Nature chemistry 2013, 6, 65-74. (9) Hofmann, J.; Hahm, H. S.; Seeberger, P. H.; Pagel, K. Nature 2015, 526, 241-244. (10) Yang, H. M.; Shi, L.; Zhuang, X. Y.; Su, R.; Wan, D. B.; Song, F. R.; Li, J. Y.; Liu, S. Y. Scientific Reports 2016, 6, 28079. (11) Hofmann, J.; Pagel, K. Angew Chem Int Edit 2017, 56, 8342-8349. (12) Simoes, J.; Domingues, P.; Reis, A.; Nunes, F. M.; Coimbra, M. A.; Domingues, R. M. Analytical chemistry 2007, 79, 5896-5905. (13) Kuki, A.; Szabo, K. E.; Nagy, L.; Zsuga, M.; Keki, S. Journal of mass spectrometry : JMS 2013, 48, 1276-1280. (14) Yuan, H.; Ying, J.; Deng, P.; Chen, P.; Shi, J.; Liu, Y.; Gao, X.; Zhao, Y. The Analyst 2015, 140, 7965-7973. (15) Stefan, S. E.; Ehsan, M.; Pearson, W. L.; Aksenov, A.; Boginski, V.; Bendiak, B.; Eyler, J. R. Analytical chemistry 2011, 83, 8468-8476. (16) Tan, Y.; Polfer, N. C. Journal of the American Society for Mass Spectrometry 2015, 26, 359-368. (17) Wan, D. B.; Yang, H. M.; Yan, C. Y.; Song, F. R.; Liu, Z. Q.; Liu, S. Y. Talanta 2013, 115, 870-875. (18) Boutegrabet, L.; Kanawati , B.; Gebefügi, I.; Peyron, D.; Cayot, P.; Gougeon, R. D.; Schmitt-Kopplin , P. Chemistry A European Journal 2012, 18, 13059-13067.

Page 6 of 7

(19) Guan, B.; Cole, R. B. Journal of the American Society for Mass Spectrometry 2008, 19, 1119-1131. (20) Guan, B.; Cole, R. B. Rapid Communications in Mass Spectrometry 2007, 21, 3165-3168. (21) Fang, T. T.; Zirrolli, J.; Bendiak, B. Carbohydrate research 2007, 342, 217-235. (22) Fang, T. T.; Bendiak, B. Journal of the American Chemical Society 2007, 129, 9721-9736. (23) Konda, C.; Bendiak, B.; Xia, Y. Journal of the American Society for Mass Spectrometry 2012, 23, 347-358. (24) Zaia, J.; Miller, M. J. C.; Seymour, J. L.; Costello, C. E. Journal of the American Society for Mass Spectrometry 2007, 18, 952-960. (25) Struwe, W. B.; Baldauf, C.; Hofmann, J.; Rudd, P. M.; Pagel, K. Chemical communications 2016, 52, 12353-12356. (26) Jiang, Y.; Cole, R. B. Journal of the American Society for Mass Spectrometry 2005, 16, 60-70. (27) Yamagaki, T.; Suzuki, H.; Tachibana, K. Journal of the American Society for Mass Spectrometry 2006, 17, 67-74. (28) Yang, S.; Yuan, W.; Yang, W.; Zhou, J.; Harlan, R.; Edwards, J.; Li, S.; Zhang, H. Analytical chemistry 2013, 85, 8188-8195. (29) Fouquet, T.; Charles, L. Journal of the American Society for Mass Spectrometry 2010, 21, 60-67. (30) Augusti, D. V.; Carazza, F.; Augusti, R.; Tao, W. A.; Cooks, R. G. Analytical chemistry 2002, 74, 3458-3462. (31) Major, M.; Fouquet, T.; Charles, L. Journal of the American Society for Mass Spectrometry 2011, 22, 1252-1259. (32) Tao, W. A.; Cooks, R. G. Angew Chem Int Edit 2001, 40, 757-760. (33) Lee, H. H. L.; Lee, J. W.; Jang, Y.; Ko, Y. H.; Kim, K.; Kim, H. I. Angew Chem Int Edit 2016, 55, 8249-8253. (34) Asakawa, D.; Smargiasso, N.; De Pauw, E. Analytical chemistry 2012, 84, 7463-7468. (35) Nishimura, S.; Niikura, K.; Kurogochi, M.; Matsushita, T.; Fumoto, M.; Hinou, H.; Kamitani, R.; Nakagawa, H.; Deguchi, K.; Miura, N.; Monde, K.; Kondo, H. Angewandte Chemie 2004, 44, 91-96. (36) Yamagaki, T.; Suzuki, H.; Tachibana, K. Journal of Mass Spectrometry 2006, 41, 454-462. (37) Chen, R.; Xu, W.; Xiong, C.; Zhou, X.; Xiong, S.; Nie, Z.; Mao, L.; Chen, Y.; Chang, H. C. Analytical chemistry 2012, 84, 465-469. (38) Wang, J. N.; Qiu, S. L.; Chen, S. M.; Xiong, C. Q.; Liu, H. H.; Wang, J. Y.; Zhang, N.; Hou, J.; He, Q.; Nie, Z. X. Analytical chemistry 2015, 87, 422-430. (39) Kurogochi, M.; Matsushita, T.; Nishimura, S. I. Angew Chem Int Edit 2004, 43, 4071-4075. (40) Suckau, D.; Resemann, A.; Schuerenberg, M.; Hufnagel, P.; Franzen, J.; Holle, A. Analytical and bioanalytical chemistry 2003, 376, 952-965. (41) Avetisyan, A.; Jensen, J. B.; Huser, T. Analytical chemistry 2013, 85, 7264-7270. (42) Jensen, J. B.; Peters, N. K.; Bhuvaneswari, T. V. Journal of Bacteriology 2002, 184, 2978-2986.


6

Page 7 of 7 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


TOC


7

Differentiation and Relative Quantitation of Disaccharide Iso-mers by

Recommend Documents