Neelakandha S. Mani
Johnson & Johnson Pharmaceutical Research and Development
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Neelakandha S. Mani.
Nature | 2011
Changlu Liu; Xia V. Yang; Jiejun Wu; Chester Kuei; Neelakandha S. Mani; Li Zhang; Jingxue Yu; Steven W. Sutton; Ning Qin; Homayon Banie; Lars Karlsson; Siquan Sun; Timothy W. Lovenberg
EBI2 (also called GPR183) is an orphan G-protein-coupled receptor that is highly expressed in spleen and upregulated upon Epstein–Barr-virus infection. Recent studies indicated that this receptor controls follicular B-cell migration and T-cell-dependent antibody production. Oxysterols elicit profound effects on immune and inflammatory responses as well as on cholesterol metabolism. The biological effects of oxysterols have largely been credited to the activation of nuclear hormone receptors. Here we isolate oxysterols from porcine spleen extracts and show that they are endogenous ligands for EBI2. The most potent ligand and activator is 7α,25-dihydroxycholesterol (OHC), with a dissociation constant of 450 pM for EBI2. In vitro, 7α,25-OHC stimulated the migration of EBI2-expressing mouse B and T cells with half-maximum effective concentration values around 500 pM, but had no effect on EBI2-deficient cells. In vivo, EBI2-deficient B cells or normal B cells desensitized by 7α,25-OHC pre-treatment showed reduced homing to follicular areas of the spleen. Blocking the synthesis of 7α,25-OHC in vivo with clotrimazole, a CYP7B1 inhibitor, reduced the content of 7α,25-OHC in the mouse spleen and promoted the migration of adoptively transferred pre-activated B cells to the T/B boundary (the boundary between the T-zone and B-zone in the spleen follicle), mimicking the phenotype of pre-activated B cells from EBI2-deficient mice. Our results show an unexpected causal link between EBI2, an orphan G-protein-coupled receptor controlling B-cell migration, and the known immunological effects of certain oxysterols, thus uncovering a previously unknown role for this class of molecules.
Green Chemistry | 2006
Xiaohu Deng; Neelakandha S. Mani
A facile, environmentally benign synthesis of sulfonamides under dynamic pH control in aqueous media is described. This methodology uses equimolar amounts of amino compounds and arylsulfonyl chlorides and omits the use of organic bases. Isolation of products involves only filtration after acidification. Excellent yields and purity were obtained without further purification.
Tetrahedron-asymmetry | 2000
Neelakandha S. Mani; Min Wu
Abstract An efficient synthetic route to non-racemic chiral 4-alkyl-1,2,3,4-tetrahydroquinoline is described. (4 R )-4-Ethyl-1,2,3,4-tetrahydroquinoline was obtained by the organoaluminum promoted modified Beckmann rearrangement involving the oxime sulfonate of (3 R )-3-ethylindan-1-one. The required optically active indanone was obtained via an asymmetric conjugate reduction of ( E )-ethyl 3-phenylpent-2-enoate.
Bioorganic & Medicinal Chemistry Letters | 2010
Alice Lee-Dutra; Danielle K. Wiener; Kristen L. Arienti; Jing Liu; Neelakandha S. Mani; Michael K. Ameriks; Frank U. Axe; Damara Gebauer; Pragnya J. Desai; Steven Nguyen; Mike Randal; Robin L. Thurmond; Siquan Sun; Lars Karlsson; James P. Edwards; Todd K. Jones; Cheryl A. Grice
A series of pyrazole-based thioethers were prepared and found to be potent cathepsin S inhibitors. A crystal structure of 13 suggests that the thioether moiety may bind to the S3 pocket of the enzyme. Additional optimization led to the discovery of aminoethylthioethers with improved enzymatic activity and submicromolar cellular potency.
Journal of Medicinal Chemistry | 1999
Lawrence G. Hamann; Neelakandha S. Mani; Robert L. Davis; Xiao-Ning Wang; Keith B. Marschke; Todd K. Jones
Journal of Medicinal Chemistry | 2006
Arjan van Oeveren; Mehrnouch Motamedi; Neelakandha S. Mani; Keith B. Marschke; Francisco J. Lopez; William T. Schrader; and Andrés Negro-Vilar; Lin Zhi
European Journal of Organic Chemistry | 2010
Xiaohu Deng; Neelakandha S. Mani
Tetrahedron-asymmetry | 2005
Xiaohu Deng; Neelakandha S. Mani
Organic and Biomolecular Chemistry | 2011
Jing Liu; Xiaohu Deng; Anne E. Fitzgerald; Zachary S. Sales; Hariharan Venkatesan; Neelakandha S. Mani
Tetrahedron Letters | 2010
Laurent Gomez; Jiejun Wu; Neelakandha S. Mani; Sudip Basu; Josef Moravek; J. Guy Breitenbucher