Computer-Guided Design, Synthesis, and Protein Kinase C Affinity of a New. Salicylate-Based Class of Bryostatin Analogs

被引：28
|
作者：
Wender, Paul A. [1 ]
Nakagawa, Yu
Near, Katherine E.
Staveness, Daryl
机构：
[1] Stanford Univ, Dept Chem, Stanford, CA 94305 USA
来源：
ORGANIC LETTERS | 2014年 / 16卷 / 19期
基金：
美国国家科学基金会; 美国国家卫生研究院;
关键词：
PHORBOL ESTER PHARMACOPHORE; STRUCTURAL BASIS; ACTIVATION; PKC; AGENTS; ALPHA; STEP;
D O I：
10.1021/ol502491f
中图分类号：
O62 [有机化学];
学科分类号：
070303 ; 081704 ;
摘要：
Bryostatin 1 is in clinical trials for the treatment of cancer and alzheimer disease and is a candidate for a first in class approach to HIV/AIDS eradication. It is neither readily available nor optimally suited for clinical use. Using a funciton oriented synthesis strategy, a new class of bryostatin inspired analog was designed with a simplified salicylate-derived subunit, enabling step economical synthesis (23 total steps) of agents exhibiting bryostatin like affinity to protein kinase C (PKC).
引用
收藏
页码：5136 / 5139
页数：4
相关论文
共 25 条
  • [1] Selectivity in translocation of protein kinase C isoforms by new analogs of bryostatin.
    Wender, PA
    Baryza, JL
    Brenner, SE
    Craske, ML
    Clarke, MO
    Horan, JC
    Mayweg, AVW
    Meyer, T
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2004, 227 : U70 - U70
  • [2] SYNTHESIS OF INGENOL ANALOGS WITH AFFINITY FOR PROTEIN-KINASE-C
    WINKLER, JD
    HONG, EC
    BAHADOR, A
    KAZANIETZ, MG
    BLUMBER, PM
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1993, 3 (04) : 577 - 580
  • [3] Improved Protein Kinase C Affinity through Final Step Diversification of a Simplified Salicylate-Derived Bryostatin Analog Scaffold
    Wender, Paul A.
    Staveness, Daryl
    ORGANIC LETTERS, 2014, 16 (19) : 5140 - 5143
  • [4] Synthesis and biological evaluation of a new class of bryostatin analogues: the role of the C20 substituent in protein kinase C binding
    Wender, PA
    Hinkle, KW
    TETRAHEDRON LETTERS, 2000, 41 (35) : 6725 - 6729
  • [5] The design, synthesis, and evaluation of C7 diversified bryostatin analogs reveals a hot spot for PKC affinity
    Wender, Paul A.
    Verma, Vishal A.
    ORGANIC LETTERS, 2008, 10 (15) : 3331 - 3334
  • [6] Structure-based design of a new class of protein kinase C modulators
    Qiao, LX
    Wang, SM
    George, C
    Lewin, NE
    Blumberg, PM
    Kozikowski, AP
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1998, 120 (26) : 6629 - 6630
  • [7] Design, synthesis, and evaluation of a new class of protein kinase C modulators as prostate cancer inhibitors.
    Zhao, LY
    Qiao, LX
    Rong, SB
    Wu, XW
    Wang, SM
    Tian, J
    Glazer, RI
    Savage, J
    Roth, B
    Kozikowski, AP
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2000, 220 : U545 - U545
  • [8] Synthesis and characterization of new photolabile phorbol esters for affinity labeling of protein kinase C
    Irie, K
    Ishii, T
    Ohigashi, H
    Wender, PA
    Miller, BL
    Takeda, N
    JOURNAL OF ORGANIC CHEMISTRY, 1996, 61 (06): : 2164 - 2173
  • [9] METHODOLOGY FOR THE SYNTHESIS OF 3-OXYGENATED INGENANES - THE FIRST INGENOL ANALOGS WITH HIGH-AFFINITY FOR PROTEIN-KINASE-C
    WINKLER, JD
    HONG, BC
    BAHADOR, A
    KAZANIETZ, MG
    BLUMBERG, PM
    JOURNAL OF ORGANIC CHEMISTRY, 1995, 60 (05): : 1381 - 1390
  • [10] Design and synthesis of protein kinase Cα activators based on 'out of pocket' interactions
    Hirai, Go
    Ohkubo, Megumi
    Tamura, Yuki
    Sodeoka, Mikiko
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2011, 21 (12) : 3587 - 3590
123