The Chemistry Core will provide essential chemistry support for this Research Program through the synthesis and analysis of the specific novel lipid mediators being studied. This Core will be responsible for the chemical synthesis of the required quantities (up to milligram-scale) of a panel of bioactive lipoxins, resolvins, docosatrienes, presqualene diphosphate derivatives and related lipid mediators that will be used to study their role in the resolution of inflammation associated with periodontal disease. The Chemistry Core will develop and optimize the required synthetic pathways for the preparation of the selected lipid mediators in a stereochemically pure form and will carry out their total synthesis, detailed purification and structural verification. The Chemistry Core will also collaborate closely with the other Sub-Projects on the identification, structural elucidation and study of the targeted lipid mediators and will help prepare isotopically labeled derivatives for receptor binding studies. Overall, the work performed in the Chemistry Core is essential for studying the key actions of the lipid mediators studied in this Program, for elucidating the their role in the signaling pathways involved in resolution, and for establishing their potential """"""""pro-resolution"""""""" and anti-inflammatory roles.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Specialized Center (P50)
Project #
5P50DE016191-02
Application #
7091616
Study Section
Special Emphasis Panel (ZDE1)
Project Start
Project End
Budget Start
2005-08-01
Budget End
2006-07-31
Support Year
2
Fiscal Year
2005
Total Cost
$170,669
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Van Dyke, T E; Hasturk, H; Kantarci, A et al. (2015) Proresolving nanomedicines activate bone regeneration in periodontitis. J Dent Res 94:148-56
Winkler, Jeremy W; Uddin, Jasim; Serhan, Charles N et al. (2013) Stereocontrolled total synthesis of the potent anti-inflammatory and pro-resolving lipid mediator resolvin D3 and its aspirin-triggered 17R-epimer. Org Lett 15:1424-7
Gao, Li; Faibish, Dan; Fredman, Gabrielle et al. (2013) Resolvin E1 and chemokine-like receptor 1 mediate bone preservation. J Immunol 190:689-94
Bartold, P Mark; Van Dyke, Thomas E (2013) Periodontitis: a host-mediated disruption of microbial homeostasis. Unlearning learned concepts. Periodontol 2000 62:203-17
Petasis, Nicos A; Yang, Rong; Winkler, Jeremy W et al. (2012) Stereocontrolled total synthesis of neuroprotectin D1 / protectin D1 and its aspirin-triggered stereoisomer. Tetrahedron Lett 53:1695-1698
Hasturk, Hatice; Kantarci, Alpdogan; Van Dyke, Thomas E (2012) Paradigm shift in the pharmacological management of periodontal diseases. Front Oral Biol 15:160-76
Hasturk, Hatice; Kantarci, Alpdogan; Van Dyke, Thomas E (2012) Oral inflammatory diseases and systemic inflammation: role of the macrophage. Front Immunol 3:118
Schif-Zuck, Sagie; Gross, Nufar; Assi, Simaan et al. (2011) Saturated-efferocytosis generates pro-resolving CD11b low macrophages: modulation by resolvins and glucocorticoids. Eur J Immunol 41:366-79
MacManus, Christopher F; Campbell, Eric L; Keely, Simon et al. (2011) Anti-inflammatory actions of adrenomedullin through fine tuning of HIF stabilization. FASEB J 25:1856-64
Serhan, Charles N; Petasis, Nicos A (2011) Resolvins and protectins in inflammation resolution. Chem Rev 111:5922-43

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