Conformationally constrained analogues of diacylglycerol. 18. The incorporation of a hydroxamate moiety into diacylglycerol-lactones reduces lipophilicity and helps discriminate between sn-1 and sn-2 binding modes to protein kinase C (PK-C). Implications for isozyme specificity

Journal of Medicinal Chemistry

Volumn 44, Issue 25, 2001, Pages 4309-4312

  Lee, J ^a   Marquez, V E ^a   Han, K C ^a   Kang, J H ^a   Pearce, L L ^b   Lewin, N E ^b   Yan, S ^c   Benzaria, S ^c   Nicklaus, M C ^c   Blumberg, P M ^b  

^a Seoul National University   (South Korea)

^b NATIONAL CANCER INSTITUTE   (United States)

^c NATIONAL CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; DIACYLGLYCEROL DERIVATIVE; LACTONE DERIVATIVE;

ANTINEOPLASTIC ACTIVITY; ARTICLE; BINDING AFFINITY; DRUG DESIGN; DRUG POTENCY; DRUG PROTEIN BINDING; ENZYME ACTIVATION; ENZYME SPECIFICITY; HUMAN; HUMAN CELL; LIPOPHILICITY; STRUCTURE ACTIVITY RELATION;

4-BUTYROLACTONE; DIGLYCERIDES; DRUG DESIGN; HYDROXAMIC ACIDS; ISOENZYMES; LACTONES; LIGANDS; MODELS, MOLECULAR; MOLECULAR CONFORMATION; PROTEIN BINDING; PROTEIN KINASE C; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0035818887     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0103965     Document Type: Article

References (13)

1. Direct visualization of the translocation of the γ-subspecies of protein kinase C in living cells using fusion proteins with green fluorescent protein
2. Green fluorescent protein (GFP)-tagged cysteine-rich domains from protein kinase C as fluorescent indicators for diacylgylcerol signaling in living cells
3. Phosphatidyl-L-serine is necessary for protein kinase C's high affinity interaction with diacylglycerol-containing membranes
4. Regulation of protein kinase C
5. Competitive inhibition by diacylglycerol of specific phorbol ester binding
6. The transition from a pharmacophore-guided approach to a receptor-guided approach in the design of potent kinase C ligands
7. Conformationally constrained analogues of diacylglycerol (DAG). 16. How much structural complexity is necessary for recognition and high binding affinity to protein kinase C?
8. Crystal structure of the cys2 activator-binding domain of protein kinase C delta in complex with phorbol ester
9. An optimized protein kinase C activating diacylglycerol combining high binding affinity (Ki) with reduced lipophilicity (log P)
10. KOWWIN 1.63
11. Distributed automatic docking of flexible ligands to proteins: Parallel applications of autodock 2.4
12. DAG-lactones, a new class of PKC agonists, induce apoptosis in LNCaP prostate cancer cells by selective activation of PKCα
13. Characterization of ligand and substrate specificity for the calcium-dependent and calcium-independent protein kinase-C isozymes