| Title |
Top Down Tandem Mass Spectrometric Analysis of a Chemically Modified Rough-Type Lipopolysaccharide Vaccine Candidate
|
|---|---|
| Published in |
Journal of the American Society for Mass Spectrometry, February 2018
|
| DOI | 10.1007/s13361-018-1897-y |
| Pubmed ID | |
| Authors |
Benjamin L. Oyler, Mohd M. Khan, Donald F. Smith, Erin M. Harberts, David P. A. Kilgour, Robert K. Ernst, Alan S. Cross, David R. Goodlett |
| Abstract |
Recent advances in lipopolysaccharide (LPS) biology have led to its use in drug discovery pipelines, including vaccine and vaccine adjuvant discovery. Desirable characteristics for LPS vaccine candidates include both the ability to produce a specific antibody titer in patients and a minimal host inflammatory response directed by the innate immune system. However, in-depth chemical characterization of most LPS extracts has not been performed; hence, biological activities of these extracts are unpredictable. Additionally, the most widely adopted workflow for LPS structure elucidation includes nonspecific chemical decomposition steps before analyses, making structures inferred and not necessarily biologically relevant. In this work, several different mass spectrometry workflows that have not been previously explored were employed to show proof-of-principle for top down LPS primary structure elucidation, specifically for a rough-type mutant (J5) E. coli-derived LPS component of a vaccine candidate. First, ion mobility filtered precursor ions were subjected to collision induced dissociation (CID) to define differences in native J5 LPS v. chemically detoxified J5 LPS (dLPS). Next, ultra-high mass resolving power, accurate mass spectrometry was employed for unequivocal precursor and product ion empirical formulae generation. Finally, MS3analyses in an ion trap instrument showed that previous knowledge about dissociation of LPS components can be used to reconstruct and sequence LPS in a top down fashion. A structural rationale is also explained for differential inflammatory dose-response curves, in vitro, when HEK-Blue hTLR4 cells were administered increasing concentrations of native J5 LPS v. dLPS, which will be useful in future drug discovery efforts. Graphical Abstract ᅟ. |
X Demographics
The data shown below were collected from the profiles of 8 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 3 | 38% |
| Australia | 1 | 13% |
| Canada | 1 | 13% |
| Taiwan | 1 | 13% |
| Unknown | 2 | 25% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 4 | 50% |
| Scientists | 3 | 38% |
| Science communicators (journalists, bloggers, editors) | 1 | 13% |
Mendeley readers
The data shown below were compiled from readership statistics for 24 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 24 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 4 | 17% |
| Student > Ph. D. Student | 4 | 17% |
| Student > Master | 3 | 13% |
| Student > Bachelor | 2 | 8% |
| Other | 2 | 8% |
| Other | 5 | 21% |
| Unknown | 4 | 17% |
| Readers by discipline | Count | As % |
|---|---|---|
| Chemistry | 9 | 38% |
| Agricultural and Biological Sciences | 3 | 13% |
| Biochemistry, Genetics and Molecular Biology | 3 | 13% |
| Medicine and Dentistry | 1 | 4% |
| Materials Science | 1 | 4% |
| Other | 0 | 0% |
| Unknown | 7 | 29% |
Attention Score in Context
This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 August 2019.
All research outputs
#7,208,166
of 25,382,440 outputs
Outputs from Journal of the American Society for Mass Spectrometry
#969
of 3,835 outputs
Outputs of similar age
#118,476
of 344,345 outputs
Outputs of similar age from Journal of the American Society for Mass Spectrometry
#8
of 59 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. This one has received more attention than most of these and is in the 71st percentile.
So far Altmetric has tracked 3,835 research outputs from this source. They receive a mean Attention Score of 3.8. This one has gotten more attention than average, scoring higher than 73% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 344,345 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 65% of its contemporaries.
We're also able to compare this research output to 59 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 79% of its contemporaries.