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), Vol. 27:19; ISSN 0006-2960
• Country of Publication: United States
• Language: English

Related Subjects

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