Gas-Phase Fragmentation for Oligonucleotide Sequencing

Several gas-phase sequencing techniques have attained success all rely on the generation and mass analysis of sequence-specific fragment ions [38-40], These methods have the advantage of simplicity and are potentially faster than solution-phase methods. 

Several ion activation techniques have been used to determine the gas-phase fragmentation behavior of oligonucleotides [41-49], These studies have concluded that the loss of a base is a dominant fragmentation, and occurs via a 

In any gas-phase procedure, oligonucleotide sequencing is accomplished either by accounting lo-type ion series alone or (a — B )- and w-type complementary ion series both. These complementary ions can provide bidirectional sequencing. The (a - B )-ions build a sequence from 5 3 direction, whereas the w-ions provide the sequence from the 3 5 direction. The following techniques have been developed to sequence oligonucleotides. 

ESI-Infrared Multiphoton Dissociation IRMPD of ESI-generated ions can also provide sequence information. By combining the data from the nozzle-skimmer dissociation and IRMPD experiments, nearly complete sequence coverage for larger oligonucleotides can be obtained [48]. These two dissociation techniques yield complementary sequence ions. For example, IRMPD primarily produces w- and (a — B )-type sequence ions, whereas the nozzle-skimmer dissociation generates b-, c-, and f-type ions. 

MALDI Post-Source Decay The fast-metastable fragmentations have a decaytime constant on the order of the acceleration event and are considered a nuisance for the MALDI-TOF-MS analysis of large oligonucleotides. In contrast, the 

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