MASS SPECTROMETRY OF ANTIGENIC LIPOPEPTIDES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 从一家商业公司获得了一种脂肽的合成版本，它是最早出现在艾滋病毒感染细胞中的化合物之一，并使用来自艾滋病毒患者捐赠者的细胞来生成T细胞系。进一步分析发现，合成的靶向脂肽不是纯的，而是一种混合物，而且靶向脂肽不是抗原性的，而是发现了两个新的抗原性成分。质谱学研究表明，新的抗原组分在结构上彼此非常相似，并且具有与预期合成结构相似的结构。BUSM MS资源的质谱学研究包括使用GC/MS、MALDI和ESI Q-o-TOF和MALDI和ESI-FTMS仪器，以及已知和未知化合物的酶消化和化学水解。现在已经解决了结构问题；合成了类似物，并测试了它们的生物活性。描述这一阶段研究的手稿最近发表(I Van Rhijn等人，CD1c绕过溶酶体提呈具有12个氨基酸的脂肽抗原。医生：J Exp Med，J Exp Med2009、206、1409-1422。这份报告补充了最近发表的另一份关于CD1a脂肽抗原的合成和生物测试的报告。(DC Young等人，由CD1a提出的双脱氧肌球蛋白抗原的合成揭示了T细胞对天然脂肽结构的精细特异性。J生物化学。200928425087-25096。)

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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 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 recent publication 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.)