NA UGM24: MS analysis of intact oligonucleotides

This webinar covers the topic of intact oligonucleotide analysis, a rapidly growing area in drug modalities. Marshall Bern introduces the Oligo workflow, which has been in use for nearly two years and continues to be enhanced, particularly in its MS2 annotation features. The workflow assumes a negative mode by default and is designed to handle a mass range of 2 to 30 kDa for deconvolution. It offers a unique approach to specifying oligonucleotides by allowing users to separately define the sugar, base, and linker components.

The discussion also delves into the technical specifics of oligonucleotide fragmentation, highlighting the software’s capability to handle complex spectra with high accuracy. The speaker illustrates this with examples from experiments conducted during the COVID lockdown, where oligonucleotides were analyzed using various techniques to achieve complete fragmentation. The webinar also touches on the software’s ability to differentiate between different types of linkages and modifications within the oligonucleotide chain, which is crucial for precise drug development. Additionally, the speaker compares their method to other existing techniques, demonstrating its superior ability to achieve nearly complete sequence coverage and more accurate peak annotations, which are essential for confirming the sequence integrity of long oligonucleotides in pharmaceutical research.