Structure-activity relationship of synthetic branched-chain distearoylglycerol (distearin) as protein kinase C activators

Journal Article · Tue Sep 20 00:00:00 EDT 1988 · Biochemistry; (USA)

DOI:https://doi.org/10.1021/bi00419a028· OSTI ID:6897688

Zhou, Qingzhong; Raynor, R L; Wood, Jr, M G; Menger, F M; Kuo, J F ^[1]

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1. Emory Univ., Atlanta, GA (USA)

Several representative branched-chain analogues of distearin (DS) were synthesized and tested for their abilities to activate protein kinase C (PKC) and to compete for the binding of ({sup 3}H)phorbol 12,13-dibutyrate (PDBu) to the enzyme. Substitutions of stearoyl moieties at sn-1 and sn-2 with 8-methylstearate decreased activities on these parameters, relative to those of the parental diacylglycerol DS, a weak PKC activator. Substitutions with 8-butyl, 4-butyl, or 8-phenyl derivatives, on the other hand, increased activities of the resulting analogues to levels comparable to those seen for diolein (DO), a diacylglycerol prototype shown to be a potent PKC activator. Kinetic analysis indicated that 8-methyldistearin (8-MeDS) acted by decreasing, whereas 8-butyldistearin (8-BuDS) and 8-phenyldistearin (8-PhDS) acted by increasing, the affinities of PKC for phosphatidylserine (PS, a phospholipid cofactor) and Ca{sup 2+} compared to the values seen in the absence or presence of DS. The stimulatory effect of 8-BuDS and 8-PhDS on PKC, as DO, was additive to that of 1,2-(8-butyl)distearoylphosphatidylcholine (1,2(8-Bu)DSPC) and, moreover, they abolished the marked inhibition of the enzyme activity caused by high concentrations of 1,2(8-Bu)DSPC. The present findings demonstrated a structure-activity relationship of the branched-chain DS analogues in the regulation of PKC, perhaps related to their abilities to specifically modify interactions of PKC with PS and/or Ca{sup 2+} critically involved in enzyme activation/inactivation.

• OSTI ID: 6897688
• Journal Information: Biochemistry; (USA), Journal Name: Biochemistry; (USA) Vol. 27:19; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALCOHOLS
ALDEHYDES
AMINO ACIDS
BIOCHEMICAL REACTION KINETICS
CARBOXYLIC ACIDS
CARCINOGENS
CHEMICAL REACTIONS
CROSS-LINKING
ENZYME INHIBITORS
ENZYMES
ESTERS
GLYCEROL
GLYOXYLIC ACID
HYDROGEN COMPOUNDS
HYDROXY ACIDS
HYDROXY COMPOUNDS
KINETICS
LIPIDS
LIPOPROTEINS
ORGANIC ACIDS
ORGANIC COMPOUNDS
PHORBOL ESTERS
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
POLYMERIZATION
PROTEINS
REACTION KINETICS
SERINE
STRUCTURE-ACTIVITY RELATIONSHIPS
TRANSFERASES
TRITIUM COMPOUNDS