Imidoester inhibition of lymphocyte DNA synthesis

Imidoesters amidinate free amino groups and produce inter- and intramolecular covalent bonds. To determine whether imidoesters influenced lymphocyte transformation, human peripheral blood or calf lymph node lymphocytes were cultured with dimethyladipimate (DMA), a bifunctional (cross-linking) imidoester, or methyl acetimidate (MAC), a monofunctional (noncross-linking) imidoester. Both DMA and MAC decreased the rate of endogenous DNA synthesis in a dose-dependent fashion. In further work, lymphocytes were treated with Phaseolus vulgaris phytohemagglutinin, concanavalin A, or periodate. DMA (1 mM) decreased DNA synthesis in P. vulgaris phytohemagglutinin-stimulated human cells by 65%, Concanavalin A-stimulated cells by 98.2%, and periodate-stimulated cells by 85%. Similar results were obtained with 1 mM MAC. Inhibition by DMA was slightly greater than was the inhibition by MAC. Decreased DNA synthesis resulted if DMA was added to P. vulgaris phytohemagglutinin-stimulated human lymphocytes at initiation of culture (72%) or after 16 hr (75%); inhibition was less when DMA was added after 24 hr (43%) and was not apparent if added after 48 hr. Therefore, both monofunctional and bifunctional imidoesters inhibit endogenous and stimulated DNA synthesis in human and calf lymphocytes.