An optimized protein kinase C activating diacylglycerol combining high binding affinity (Ki) with reduced lipophilicity (log P)

Journal of Medicinal Chemistry

Volumn 44, Issue 12, 2001, Pages 1892-1904

  Nacro, K ^a,b   Sigano, D M ^b   Yan, S ^b   Nicklaus, M C ^b   Pearce, L L ^c   Lewin, N E ^c   Garfield, S H ^d   Blumberg, P M ^c   Marquez, V E ^b  

^a GEORGETOWN UNIVERSITY   (United States)

^b NATIONAL CANCER INSTITUTE   (United States)

^c NATIONAL INSTITUTES OF HEALTH   (United States)

^d NATIONAL CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 (3 ISOPROPYL 4 METHYLPENTANOYL) 2 (3 METHYLBUT 2 ENOYL)GLYCEROL; 1 (3 METHYLBUT 2 ENOYL) 2 (3 ISOPROPYL 4 METHYLPENTANOYL)GLYCEROL; DIACYLGLYCEROL DERIVATIVE; GREEN FLUORESCENT PROTEIN; PROTEIN KINASE C; PROTEIN KINASE C ACTIVATOR; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; BINDING AFFINITY; CHO CELL; CONTROLLED STUDY; DRUG ACTIVITY; DRUG BINDING; DRUG SOLUBILITY; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TRANSPORT; ENZYME ACTIVATION; HYDROPHILICITY; LIPOPHILICITY; MEMBRANE TRANSPORT; MOLECULAR DYNAMICS; MOLECULAR INTERACTION; NONHUMAN; SIMULATION;

ANIMALS; BINDING SITES; BINDING, COMPETITIVE; CHO CELLS; CRICETINAE; DATABASES; DIGLYCERIDES; ENZYME ACTIVATION; HYDROGEN BONDING; KINETICS; MODELS, MOLECULAR; MOLECULAR CONFORMATION; PHORBOL 12,13-DIBUTYRATE; PROTEIN CONFORMATION; PROTEIN KINASE C; PROTEIN STRUCTURE, SECONDARY; RECOMBINANT FUSION PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIP; TRANSFECTION; TRYPTOPHAN; TYROSINE; ZINC FINGERS;

EID: 0035821598     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm010052e     Document Type: Article

References (26)

1. Protein kinase C: Structure, function and regulation
2. Regulation of protein kinase C: A tale of lipids and proteins
3. The extended protein kinase C superfamily
4. New insights into the regulation of protein kinase C. and novel phorbol ester receptors
5. Direct visualization of the translocation of the γ-subspecies of protein kinase C in living cells using fusion proteins with green fluorescent protein
6. Green fluorescent protein (GFP)-tagged cysteine-rich domains from protein kinase C as fluorescent indicators for diacylgylcerol signaling in living cells
7. Phosphatidyl-L-serine is necessary for protein kinase C's high affinity interaction with diacylglycerol-containing membranes
8. Regulation of protein kinase C
9. Intracelluar signaling by hydrolysis of phospholipids and activation of protein-kinase-C
10. Protein kinase C as a molecular machine for decoding calcium and diacylglycerol signals
11. The role of protein kinase C in G1 and G2/M phases of the cell cycle
12. Crystal structure of the cys2 activator-binding domain of protein kinase C delta in complex with phorbol ester
13. Competitive inhibition by diacylglycerol of specific phorbol ester binding
14. The transition from a pharmacophore-guided approach to a receptor-guided approach in the design of potent kinase C ligands
15. Conformationally constrained analogues of diacylglycerol (DAG). 16. How much structural complexity is necessary for recognition and high binding affinity to protein kinase C?
16. Diacylglycerols with lipophilically equivalent branched acyl chains display high affinity for protein kinase C (PK-C). A direct measure of the effect of constraining the glycerol backbone in DAG lactones
17. KOWWIN 1.63
18. Differential localization of protein kinase C delta by phorbol esters and related compounds using a fusion protein with green fluorescent protein
19. Distributed automatic docking of flexible ligands to proteins: Parallel applications of autodock 2.4
20. CHARMM: A program for macromolecular energy minimization and dynamics calculations
21. All-atom empirical potential for molecular modeling and dynamics studies of proteins
22. Quantum chemical studies of reactions of the cyclic disulfides with the zinc finger domains in the HIV-1 nucleocapsid protein (NCp7)
23. Characterization of ligand and substrate specificity for the calcium-dependent and calcium-independent protein kinase-C isozymes
24. Differential roles of the tandem C-1 domains of PKC-δ in the biphasic down-regulation induced by bryostatin 1