This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.We described a multiple-stage ion-trap mass spectrometric approach to characterize the structures of phosphatidylinositol and phosphatidyl-myoinositol mannosides (PIMs) in a complex mixture isolated from Mycobacterium bovis Bacillus Calmette Guerin. The positions of the fatty acyl substituents of PIMs on the glycerol backbone can be easily assigned, based on the findings that the ions arising from losses of the fatty acid substituent at sn-2 as molecules of acid and of ketene, respectively (i.e., the [M - H - R2CO2H]- and [M - H - R2CH=CO]- ions), are respectively more abundant than the ions arising from the analogous losses at sn-1 (i.e., forming the [M - H - R1CO2H]- and [M - H - R1CH=CO]- ions) in the MS2 product-ion spectra of the [M - H]- ions desorbed by electrospray ionization (ESI). Further dissociation of the [M - H - R2CO2H]- and [M - H - R1CO2H]- ions give rise to a pair of unique ions corresponding to losses of 74 Da and 56 Da (i.e., [M - H - RxCO2H - 56]- and [M- H - RxCO2H - 74]- ions, x=1, 2), respectively, probably arising from various losses of the glycerol. The profile of the ion-pair in the MS3 spectrum of the [M - H - R2CO2H]- ion is readily distinguishable from that in the MS3 spectrum of the [M - H - R1CO2H]- ion and thus, the assignment of the fatty acid substituents on the glycerol backbone can be confirmed. The product-ion spectra of the [M - H]- ions from 2-lyso-PIM and from 1-lyso-PIM are discernible, and both the spectra contain a unique ion that arises from primary loss of the fatty acid substituent at the glycerol backbone, followed by loss of a bicyclic glycerophosphate ester moiety of 136 Da. The combined structural information from the MS2 and MS3 production spectra permit the complex structures of PIMs that consist of various isomers to be unveiled in detail.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR000954-30
Application #
7597657
Study Section
Special Emphasis Panel (ZRG1-BPC-H (40))
Project Start
2007-02-01
Project End
2008-01-31
Budget Start
2007-02-01
Budget End
2008-01-31
Support Year
30
Fiscal Year
2007
Total Cost
$8,812
Indirect Cost
Name
Washington University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Yue, Xuyi; Dhavale, Dhruva D; Li, Junfeng et al. (2018) Design, synthesis, and in vitro evaluation of quinolinyl analogues for ?-synuclein aggregation. Bioorg Med Chem Lett 28:1011-1019
Ohlemacher, Shannon I; Giblin, Daryl E; d'Avignon, D André et al. (2017) Enterobacteria secrete an inhibitor of Pseudomonas virulence during clinical bacteriuria. J Clin Invest 127:4018-4030
Lin, Xiaobo; Racette, Susan B; Ma, Lina et al. (2017) Endogenous Cholesterol Excretion Is Negatively Associated With Carotid Intima-Media Thickness in Humans. Arterioscler Thromb Vasc Biol 37:2364-2369
Ovod, Vitaliy; Ramsey, Kara N; Mawuenyega, Kwasi G et al. (2017) Amyloid ? concentrations and stable isotope labeling kinetics of human plasma specific to central nervous system amyloidosis. Alzheimers Dement 13:841-849
Cade, W Todd; Levy, Philip T; Tinius, Rachel A et al. (2017) Markers of maternal and infant metabolism are associated with ventricular dysfunction in infants of obese women with type 2 diabetes. Pediatr Res 82:768-775
Lucey, Brendan P; Mawuenyega, Kwasi G; Patterson, Bruce W et al. (2017) Associations Between ?-Amyloid Kinetics and the ?-Amyloid Diurnal Pattern in the Central Nervous System. JAMA Neurol 74:207-215
Alvarez, Jessica A; Ziegler, Thomas R; Millson, Erin C et al. (2016) Body composition and lung function in cystic fibrosis and their association with adiposity and normal-weight obesity. Nutrition 32:447-52
Sterl, Karin; Wang, Songyan; Oestricker, Lauren et al. (2016) Metabolic responses to xenin-25 are altered in humans with Roux-en-Y gastric bypass surgery. Peptides 82:76-84
Wei, Xiaochao; Song, Haowei; Yin, Li et al. (2016) Fatty acid synthesis configures the plasma membrane for inflammation in diabetes. Nature 539:294-298
Shields-Cutler, Robin R; Crowley, Jan R; Miller, Connelly D et al. (2016) Human Metabolome-derived Cofactors Are Required for the Antibacterial Activity of Siderocalin in Urine. J Biol Chem 291:25901-25910

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