To assess the role of the amine and ester containing oligopeptide side-chains in bis-indole protein kinase C inhibitors, six novel hybrids in this series were synthesized. These new compounds displayed effective inhibitory activity against protein kinase C-α. Protein kinase C (PKC) is a member of the serine/threonine specific protein kinase family 1 which is implicated in the pathogenesis of a variety of diseases. 2 Over the past decade, regulation of this family of enzymes has generated considerable interest. One of the most informative approaches to study the role played by PKC in cellular processes is to inhibit the enzymatic activity of the kinase in intact cells. For this purpose, cell-permeable, potent and selective compounds are required. Among a variety of agents 3,13 which inhibit PKC and other protein kinases, the naturally occurring glycosylated indolocarbazole staurosporine (1)4 is the most potent, and has been modified 5 in attempts to control kinase selectivity and toxicity. The structurally simpler Arcyriarubins 6 (2: Arcyriarubin A) also inhibit PKC. 7 Recent investigations by Toullec, 8a Davis 8b and co-workers have revealed that derivatives of this class, such as compound 3 in which a dimethylamine containing side chain is attached to the indole nitrogen, are not only highly potent but also quite selective inhibitors of PKC. In the course of structure-activity studies on PKC inhibitors in this series, we wished to determine if amine or ester containing polypyrrolamide side-chains contribute to biological activity. We report here the synthesis and activity of the compounds 5-10, in which one of the hydrogen atoms attached to the nitrogen atom of the indole ring is substituted by such oligopeptide chains. Within this group of target molecules, compounds 5-7 contain a dimethylamine as a peptide terminal, while, for comparison, compounds 8-10 contain a methyl ester as a terminal group.