2013
DOI: 10.1021/ac400448t
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Top-Down Interrogation of Chemically Modified Oligonucleotides by Negative Electron Transfer and Collision Induced Dissociation

Abstract: Two sets of synthetic 21-23mer oligonucleotides with various types of 2'-position modifications have been studied with tandem mass spectrometry using ion trap collision-induced dissociation (IT-CID) and negative electron transfer (NET)-CID. A systematic study has been conducted to define the limitations of IT-CID in sequencing such 2'-chemically modified oligonucleotides. We found that IT-CID is sufficient in characterizing oligonucleotide sequences that do not contain DNA residues, where high sequence coverag… Show more

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Cited by 47 publications
(63 citation statements)
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“…A C C E P T E D ACCEPTED MANUSCRIPT 14 ligands. In addition, consistent affinity measurement between the two workflows indicated that the quick wash step involved in BFA did not cause significant ligand loss and compound recovery was achieved as completely in BFA as in UFA for these hCAI inhibitors.…”
Section: A C C E P T E D Accepted Manuscriptmentioning
confidence: 99%
See 1 more Smart Citation
“…A C C E P T E D ACCEPTED MANUSCRIPT 14 ligands. In addition, consistent affinity measurement between the two workflows indicated that the quick wash step involved in BFA did not cause significant ligand loss and compound recovery was achieved as completely in BFA as in UFA for these hCAI inhibitors.…”
Section: A C C E P T E D Accepted Manuscriptmentioning
confidence: 99%
“…Commonly used techniques for ligand binding measurement in the drug discovery and development program include nuclear magnetic resonance (NMR) [8], surface plasmon resonance (SPR) [9], fluorescence monitoring [10], isothermal titration calorimetry (ITC) [11] and differential scanning calorimetry (DSC) [12]. Apart from the aforementioned spectroscopic and biophysical methods, mass spectrometry (MS)-based techniques can provide critical insight into biomolecule structures and ligand binding properties [13][14][15][16]. Specifically, ultrafiltration-LC/MS (UF-LC/MS) has emerged as a versatile and complementary approach for protein-ligand interaction study and played an increasingly vital role in early drug discovery [17][18][19][20][21].…”
Section: Introductionmentioning
confidence: 99%
“…While most condensed-phase derivatization reactions are performed in an off-line fashion, gas-phase ion/ion reactions provide a means to manipulate ion type within the mass spectrometer, allowing rapid examination of the reaction products and facile comparison with the unmodified analytes. For example, proton transfer, 9 electron transfer 10,11 and metal ion transfer 12 reactions have been used to decouple the ion type from the ionization method, expanding the range of ion types that can be investigated by MS n . Aside from these charged particle transfer reactions, a number of approaches to covalently modify ions via a long-lived complex in the gas-phase have been developed, aiming at selectively manipulating ion types at specific functionalities.…”
Section: Introductionmentioning
confidence: 99%
“…However, relying only on the combination of the forces mentioned above will make the progress suffer from cumbersome steps, labor-intensive and incomplete immobilization because of the relatively weaker interaction. Sorts of stronger interactions based on p-p stacking interactions, hydrophobic interactions, and covalent bonding have been extensively used in order to strengthen the forces between proteins and materials [14][15][16][17][18][19][20]. Many analytical approaches and strategies have been developed to facilitate membrane protein characterization.…”
Section: Introductionmentioning
confidence: 99%