Abyssomicin 2 Reactivates Latent HIV-1 by a PKC- and HDAC-Independent Mechanism

被引：33

作者：

Leon, Brian ^{[1
]}

Navarro, Gabriel ^{[1
]}

Dickey, Bailey J. ^{[1
]}

Stepan, George ^{[2
]}

Tsai, Angela ^{[2
]}

Jones, Gregg S. ^{[2
]}

Morales, Monica E. ^{[1
]}

Barnes, Tiffany ^{[2
]}

Ahmadyar, Shekeba ^{[2
]}

Tsiang, Manuel ^{[2
]}

Geleziunas, Romas ^{[2
]}

Cihlar, Tomas ^{[2
]}

Pagratis, Nikos ^{[2
]}

Tian, Yang ^{[2
]}

Yu, Helen ^{[2
]}

Linington, Roger G. ^{[1
]}

机构：

[1] Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA

[2] Gilead Sci Inc, Dept Biol, Foster City, CA 94404 USA

来源：

ORGANIC LETTERS | 2015年 / 17卷 / 02期

关键词：

MARINE VERRUCOSISPORA STRAIN; POLYKETIDE; ACTIVATION; INHIBITOR; VIVO;

D O I：

10.1021/ol503349y

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Screening of a marine natural products library afforded three new analogues of the tetronic acid containing polyketide abyssomicin family and identified abyssomicin 2 as a selective reactivator of latent HIV virus. Examination of the mode of action of this new latent HIV reactivating agent demonstrated that it functions via a distinct mechanism compared to that of existing reactivating agents and is effective at reactivating latent virus in a subset of primary patient cell lines.

引用

页码：262 / 265

页数：4

共 27 条

[1] Highly potent, synthetically accessible prostratin analogs induce latent HIV expression in vitro and ex vivo [J].

Beans, Elizabeth J. ;

Fournogerakis, Dennis ;

Gauntlett, Carolyn ;

Heumann, Lars V. ;

Kramer, Rainer ;

Marsden, Matthew D. ;

Murray, Danielle ;

Chun, Tae-Wook ;

Zack, Jerome A. ;

Wender, Paul A. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (29) :11698-11703

[2] Non-AIDS-defining malignancies among HIV-infected patients in the highly active antiretroviral therapy era [J].

Bedimo R. .

Current HIV/AIDS Reports, 2008, 5 (3) :140-149

[3] Total synthesis and biological evaluation of (-)-atrop-abyssomicin C [J].

Bihelovic, Filip ;

Karadzic, Ivanka ;

Matovic, Radomir ;

Saicic, Radomir N. .

ORGANIC & BIOMOLECULAR CHEMISTRY, 2013, 11 (33) :5413-5424

[4] Abyssomicin C -: A polycyclic antibiotic from a marine Verrucosispora strain as an inhibitor of the p-aminobenzoic acid/tetrahydrofolate biosynthesis pathway [J].

Bister, B ;

Bischoff, D ;

Ströbele, M ;

Riedlinger, J ;

Reicke, A ;

Wolter, F ;

Bull, AT ;

Zähner, H ;

Fiedler, HP ;

Süssmuth, RD .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2004, 43 (19) :2574-2576

[5] Studies of HIV-1 latency in an ex vivo model that uses primary central memory T cells [J].

Bosque, Alberto ;

Planelles, Vicente .

METHODS, 2011, 53 (01) :54-61

[6] New ex vivo approaches distinguish effective and ineffective single agents for reversing HIV-1 latency in vivo [J].

Bullen, C. Korin ;

Laird, Gregory M. ;

Durand, Christine M. ;

Siliciano, Janet D. ;

Siliciano, Robert F. .

NATURE MEDICINE, 2014, 20 (04) :425-+

[7] Suberoylanilide Hydroxamic Acid Reactivates HIV from Latently Infected Cells [J].

Contreras, Xavier ;

Schweneker, Marc ;

Chen, Ching-Shih ;

McCune, Joseph M. ;

Deeks, Steven G. ;

Martin, Jeffrey ;

Peterlin, B. Matija .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (11) :6782-6789

[8] Formal synthesis of Abyssomicin C [J].

Couladouros, Elias A. ;

Bouzas, Emmanuel A. ;

Magos, Alexandros D. .

TETRAHEDRON, 2006, 62 (22) :5272-5279

[9]

DeChristopher BA, 2012, NAT CHEM, V4, P705, DOI [10.1038/NCHEM.1395, 10.1038/nchem.1395]

[10]

Florescu D, 2007, ANTIVIR THER, V12, P149

← 1 2 3 →