This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. A synthetic version of a lipopeptide that is one of the first compounds to appear in HIV-infected cells was obtained from a commercial company and employed to generate a T cell line, using cells from an HIV patient donor. On further analysis it was found that the synthetically produced version of the targeted lipopeptide was not pure, but in fact a mixture, and further, the targeted lipopeptide was not antigenic, but instead two novel components were found to be antigenic. Mass spectrometric investigations indicate that the new antigenic components are very similar in structure to each other and have structures similar to the intended synthetic structure. Mass spectrometric studies at the BUSM MS Resource included the use of GC/MS, MALDI and ESI Q-o-TOF and MALDI and ESI-FTMS instrumentation, enzymatic digestion and chemical hydrolysis of the known and unknown compounds. The structure has now been solved;synthetic analogs have been prepared and their biological activity has been tested. The collaborative manuscript describing this phase of the research was published recently (I Van Rhijn et al., CD1c bypasses lysosomes to present a lipopeptide antigen with 12 amino acids. J Exp Med. 2009, 206, 1409-1422. This publication complements another that reported on the synthesis and biological testing of CD1a lipopeptide antigens. (DC Young et al., Synthesis of dideoxymycobactin antigens presented by CD1a reveals T cell finespecificity for natural lipopeptide structures. (J Biol Chem. 2009, 284, 25087-25096). Ms. Madigan's thesis is exploring the enzyme pathways that underlie the mycobactin-dideoxymucobactin pathway and their relationship to the variation in lipid profiles in M. tuberculosis;Prof. Costello serves on her thesis committee.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR010888-15
Application #
8365527
Study Section
Special Emphasis Panel (ZRG1-BCMB-H (40))
Project Start
2011-06-01
Project End
2012-08-09
Budget Start
2011-06-01
Budget End
2012-08-31
Support Year
15
Fiscal Year
2011
Total Cost
$5,678
Indirect Cost
Name
Boston University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
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