The proposal seeks acquisition of a TOF mass spectrometer coupled with an HPLC for accurate mass determination of small molecules such as natural products, organometallic compounds, nucleic acids and non-polar organic synthetic intermediates that are generated in the research groups of six major NIH-supported research groups at three departments of University of California, San Diego. The HPLC-TOF will be used for determination of composition and formulas of novel natural products obtained from marine bacteria and invertebrates, characterize enzyme-catalyzed reactions of genetically-engineered polyketide synthase complexes, nucleic acids prepared with modified base and sugar components, organometallic compounds for novel carbon-carbon bond formation or for transformations of simple thermodynamically stable molecules such as CO2 and NO2. The separations capability of the LC component will allow measurements of very minor components of moderately complex fractionated natural product extracts, and 'real-time'monitoring of reaction pathways and intermediates in the biosynthesis of natural products. The instrumental specifications have been chosen to provide ionization of a broad range of sample types, from nonpolar organic intermediates to highly-charged water-soluble molecules of molecular masses up to ~2000 and small polypeptides of larger MW yet be amenable to walk-up usage in a multi-user environment.)

Public Health Relevance

Research on drug molecules is highly dependent upon high-resolution mass spectrometry for accurate measurement of the masses of molecules. The proposed instrument will expedite research in discovery of new therapies for cancer and infectious from marine organisms and development of diagnostics by a collective group over 60 associated researchers.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biomedical Research Support Shared Instrumentation Grants (S10)
Project #
1S10RR025636-01A1
Application #
7795051
Study Section
Special Emphasis Panel (ZRG1-BCMB-D (30))
Program Officer
Birken, Steven
Project Start
2010-04-22
Project End
2011-04-21
Budget Start
2010-04-22
Budget End
2011-04-21
Support Year
1
Fiscal Year
2010
Total Cost
$305,174
Indirect Cost
Name
University of California San Diego
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Jamison, Matthew T; Dalisay, Doralyn S; Molinski, Tadeusz F (2016) Peroxide Natural Products from Plakortis zyggompha and the Sponge Association Plakortis halichondrioides-Xestospongia deweerdtae: Antifungal Activity against Cryptococcus gattii. J Nat Prod 79:555-63
Jamison, Matthew T; Macho, Jocelyn; Molinski, Tadeusz F (2016) Structure-activity of antifungal compounds inspired by aminobisabolenes from the sponge Halichondria sp. Bioorg Med Chem Lett 26:5244-5246
Wang, Xiao; Duggan, Brendan M; Molinski, Tadeusz F (2015) Mollenynes B-E from the marine sponge Spirastrella mollis. Band-selective heteronuclear single quantum coherence for discrimination of bromo-chloro regioisomerism in natural products. J Am Chem Soc 137:12343-51
Sheik, Daniel A; Brooks, Lauren; Frantzen, Kristen et al. (2015) Inhibition of the enhancement of infection of human immunodeficiency virus by semen-derived enhancer of virus infection using amyloid-targeting polymeric nanoparticles. ACS Nano 9:1829-1836
Jamison, Matthew T; Molinski, Tadeusz F (2015) Antipodal crambescin A2 homologues from the marine sponge Pseudaxinella reticulata. Antifungal structure-activity relationships. J Nat Prod 78:557-61
Guan, Yinghua; Cao, Kevin J; Cantlon, Adam et al. (2015) Real-Time Monitoring of Alzheimer's-Related Amyloid Aggregation via Probe Enhancement-Fluorescence Correlation Spectroscopy. ACS Chem Neurosci 6:1503-8
Wang, Xiao; Morinaka, Brandon I; Molinski, Tadeusz F (2014) Structures and solution conformational dynamics of stylissamides G and H from the Bahamian sponge Stylissa caribica. J Nat Prod 77:625-30
Jamison, Matthew T; Boddy, Christopher N; Molinski, Tadeusz F (2014) Salvadenosine, a 5'-deoxy-5'-(methylthio) nucleoside from the Bahamian tunicate Didemnum sp. J Org Chem 79:9992-7
Stout, E Paige; Choi, Michael Y; Castro, Januario E et al. (2014) Potent fluorinated agelastatin analogues for chronic lymphocytic leukemia: design, synthesis, and pharmacokinetic studies. J Med Chem 57:5085-93
Januar, Lawrence A; Molinski, Tadeusz F (2013) Acremolin from Acremonium strictum is N(2),3-etheno-2'-isopropyl-1-methylguanine, not a 1H-azirine. Synthesis and structural revision. Org Lett 15:2370-3

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