Differential Binding Modes of Diacylglycerol (DAG) and DAG Lactones to Protein Kinase C (PK-C)

Citations Over Time

Abstract

Diacylglycerol lactones (DAG lactones), analogous to highly potent diacylglycerols (DAGs) were synthesized to demonstrate the ability of PK-C to discriminate between two differential binding modes, sn-1 and sn-2. While both sn-1 and sn-2 binding modes are allowable in terms of hydrogen bonding, it has been found that in general, DAGs prefer to bind sn-1, while the corresponding analogous DAG lactones prefer to bind sn-2. However, this binding orientation can be directly influenced by the disposition and nature of the acyl substituent, particularly if it is highly branched. When the "binding driving force" (i.e., the larger branched acyl chain) is in the sn-2 position, a dramatic increase in binding affinity is observed in the DAG lactone as compared to its open chain DAG counterpart. As these analogous DAGs and DAG lactones have almost identical log P values, this difference in binding affinity is a direct result of the entropic advantage of constraining the glycerol backbone.

Related Papers

• → Synthesis of 1-Substituted and 1-Unsubstituted 4-Sulfonamid0-1H-pyrazol-5(2H)-ones(1996)9 cited
• → Photoreaction of 2-morpholinoacrylonitrile with substituted 1-acetonaphthones. Part II(2001)8 cited
• → ChemInform Abstract: Toward the Synthesis of Caraphenol C (VI): Substituent Effect on the Nazarov Cyclization of 2‐Arylchalcones.(2008)2 cited
• → ChemInform Abstract: Substituent Effects on the Electron Affinities of Perfluorobenzenes C6F5X(1989)
• → ChemInform Abstract: Substituent Effects on η2‐Coordinated Arene Complexes of Pentaammineosmium(II).(1988)