On the specificity of cyclodextrin complexes detected by electrospray mass spectrometry

Glycans, a family of compounds often attached to proteins and ceramides, are diverse molecules involved in a wide range of biological functions. Their structural analysis is necessary and is often carried out at the microscale level. Methods based on mass spectrometry are therefore used, although they do not provide information regarding isomeric structures often found in glycan structures. If one finds "factors" characteristic of a certain isomer, this information can be used to elucidate an unknown oligosaccharide sequence. One potential technique is to use energy-resolved mass spectrometry (ERMS) that has been used to distinguish a pair of isomeric compounds. Thus, compounds in a combinatorial library might be effectively used for this purpose. We analyzed a set of 16 isomeric disaccharides, the structures of which consisted of all possible combinations of anomeric configurations and interglycosidic linkage positions. All of the compounds were distinguished based on ERMS where normal collision-induced dissociation could distinguish only seven compounds. Furthermore, it was shown that ␣-glycosidic linkages of fucose were more reactive than the ␣ ␤-isomers and the secondary glycosides were more reactive than the primary . The structural characteristics of oligosaccharides are quite different from those of other biopolymers such as nucleic acids and peptides. The diversity is generated from sequential combination in the latter two types of polymers, whereas anomers, ring size, linkage position, branching, and sequence are factors in the case of oligosaccharides [2]. Furthermore, the regulatory mechanisms for oligosaccharides still need to be clarified and synthesis, which is not template dependent, thus creates further molecular diversity called glycoforms. Despite the difficulties encountered in structural determination, there are reports on how glycosylation as a type of posttranslational modification (PTM) of protein affects glycoprotein secretion [3,4].

Section: Erms Analysismentioning

confidence: 99%

Discrimination of 16 structural isomers of fucosyl galactoside based on energy-resolved mass spectrometry

Daikoku

Ako

Kato

et al. 2007

“…In the present experiments the formation of nonspecific adducts can't be precluded, but in any case their effect on the performed experiments did not affect the calculations, as shown from the excellent linearity of eq 8 and the agreement with the value obtained spectroscopically. However, in cases where nonspecific aggregation occurs in a high degree, the study of these complexes by using the total intensity may appear to be tricky and therefore it is proposed to apply the method presented by Gabelica and coworkers [43] to estimate the contribution of nonspecific adducts. The formation of 2:2 guest:CD complexes can not be precluded, although the features of the selected guests minimize this possibility.…”

Section: Resultsmentioning

confidence: 99%

Efficient determination and evaluation of model cyclodextrin complex binding constants by electrospray mass spectrometry

Dotsikas

Loukas

2003

Electrospray ionization mass spectrometry (ESI-MS) is now routinely used for the detection of cyclodextrin noncovalent complexes, complementing previously established methods. Hostguest complexes formed in solution are also stable for characterization by ESI in the gas phase. This paper reports the first investigations to characterize the stability of three inclusion complexes between ␤-cyclodextrin (␤-CD) and three model "guest" molecules, by determining the cyclodextrin compound complex stability constant (K st ) with the use of mass spectrometric studies. The relative signal intensity of the complexes were monitored in the positive ion mode by mixing each "guest" molecule with an up to 50-fold molar excess of ␤CD. A novel linear equation, similar to Benesi-Hildebrand, was derived allowing the determination of K st for 1:1 stoichiometry in all complexes. These values were compared with the K st obtained by spectrophotometric experiments and they were evaluated to be slightly different, indicating the validity of the described method. (J

“…A number of studies report on more or less successful analyses of noncovalent complexes where hydrophobic forces are considered to play a dominant role for the stability [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]. Liu et al [19,20] showed the preservation of hydrophobically stabilized complex between bovine β-lactoglobulin and its natural ligands, fatty acids, for the fraction of ESI-generated ions.…”

Section: Introductionmentioning

confidence: 99%

“…CDs allow for the formation of inclusion complexes with various nonpolar molecules in polar solvents [34]. Several studies have reported on the detection of inclusion complexes between CDs and aromatic or aliphatic guests, amino acids, peptides, and drugs by ESI-MS [23][24][25][26][27][28][29][30][31][32][33]. However, in these studies, guest molecules bore at least one polar group that pointed out of the cavity and enabled hydrogen bonding or dipole-dipole interactions with hydroxyls of the CD rim.…”

Section: Introductionmentioning

confidence: 99%

“…These forces become stronger in the gas phase due to the electrostatic nature and most probably dominate the complex stabilization in the absence of solvent. A large fraction of nonspecific adducts in the mass spectra of CDs bound to aliphatic ligands is a consequence of such electrostatic attraction between binding partners in the gas phase [23][24][25].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

What Happens to Hydrophobic Interactions during Transfer from the Solution to the Gas Phase? The Case of Electrospray-Based Soft Ionization Methods

Barylyuk

Balabin

Grünstein

et al. 2011

The disappearance of the hydrophobic effect in the gas phase due to the absence of an aqueous surrounding raises a long-standing question: can noncovalent complexes that are exclusively bound by hydrophobic interactions in solution be preserved in the gas phase? Some reports of successful detection by mass spectrometry of complexes largely stabilized by hydrophobic effect are questionable by the presence of electrostatic forces that hold them together in the gas phase. Here, we report on the MS-based analysis of model supramolecular complexes with a purely hydrophobic association in solution, β-cyclodextrin, and synthetic adamantyl-containing ligands with several binding sites. The stability of these complexes in the gas phase is investigated by quantum chemical methods . Compared with the free interaction partners, the inclusion complex between β-cyclodextrin and adamantyl-containing ligand is shown to be stabilized in the gas phase by ΔG = 9.6 kcal mol -1 . The host-guest association is mainly enthalpy-driven due to strong dispersion interactions caused by a large nonpolar interface and a high steric complementarity of the binding partners. Interference from other types of noncovalent binding forces is virtually absent. The complexes are successfully detected via electrospray ionization mass spectrometry, although a high dissociation yield is also observed. We attribute this pronounced dissociation of the complexes to the collisional activation of ions in the atmospheric interface of mass spectrometer. The comparison of several electrospray-based ionization methods reveals that cold spray ionization provides the softest ion generation conditions for these complexes.