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Báo cáo khoa học: Membrane anchoring of diacylglycerol lactones substituted with rigid hydrophobic acyl domains correlates with biological activities

Tham khảo luận văn - đề án 'báo cáo khoa học: membrane anchoring of diacylglycerol lactones substituted with rigid hydrophobic acyl domains correlates with biological activities', luận văn - báo cáo, báo cáo khoa học phục vụ nhu cầu học tập, nghiên cứu và làm việc hiệu quả | Membrane anchoring of diacylglycerol lactones substituted with rigid hydrophobic acyl domains correlates with biological activities Or Raifman1 Sofiya Kolusheva1 Maria J. Comin2 Noemi Kedei3 Nancy E. Lewin3 Peter M. Blumberg3 Victor E. Marquez2 and Raz Jelinek1 1 Department of Chemistry Ben Gurion University Beer Sheva Israel 2 Laboratory of MedicinalChemistry Center for Cancer Research NationalCancer Institute at Frederick NationalInstitutes of Health Frederick MD USA 3 Laboratory of Cancer Biology and Genetics Center for Cancer Research NationalCancer Institute Bethesda MD USA Keywords biomimetic membranes diacylglycerol diacylglycerol lactones DAG-lactones membrane interactions PKC translocation Correspondence V. E. Marquez Laboratory of Medicinal Chemistry Center for Cancer Research National Cancer Institute at Frederick NationalInstitutes of Health 376 Boyles Street Frederick MD 21702 USA Fax 1 3018466033 Tel 1 3018465954 E-mail marquezv@dc37a.nci.nih.gov R. Jelinek Department of Chemistry Ben Gurion University Beer Sheva 84105 Israel Fax 972 86472943 Tel 972 86461747 E-mail razj@bgu.ac.il Received 27 August 2009 revised 15 October 2009 accepted 4 November 2009 doi 10.1111 j.1742-4658.2009.07477.x Synthetic diacylglycerol lactones DAG lactones are effective modulators of critical cellular signaling pathways downstream of the lipophilic second messenger diacylglycerol that activate a host of protein kinase C PKC isozymes as well as other non-kinase proteins that share with PKC similar C1 membrane-targeting domains. A fundamental determinant of the biological activity of these amphiphilic molecules is the nature of their interactions with cellular membranes. This study characterizes the membrane interactions and bilayer anchoring of a series of DAG lactones in which the hydrophobic moiety is a molecular rod namely a rigid 4- 2- R-phenyl ethynyl benzoate moiety in the acyl position. Use of assays employing chromatic biomimetic vesicles and biophysical techniques