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The log K, AH, and TAS values for interactions of Na+, K+, Cu2+, and Ca2+ with a series of , '-dipivot lariat ethers have been determined from calorimetric titration data valid in 9:1 (v/v) CH3OH/H2O and absolute methanol at 25.0 °C. Complex stability is increased greatly by introducing pendant arms containing oxygen or nitrogen atoms to the parent macrocycles. The enthalpy and entropy changes support the idea that the side arms interact with the cations. Formation of complexes of Ca2+ is both enthalpy and entropy stabilized. All other interactions are enthalpy driven, and the entropy changes are unfavorable. Effects of pendant-arm length and substituents on the complexation of the cations are discussed on the basis of the thermodynamic data. The large negative AH values for complexation of Cu2+ with lariat ethers indicate a strong interaction between Cu2+ and the nitrogen atoms of the ligands. Large entropic losses for some of the cation-ligand interactions indicate that the lariat ethers are flexible and readily change their conformations to accommodate the cations.

Hyperactivation of AKT plays a critical role in the survival and proliferation of cancer cells. However, the molecular mechanisms underlying AKT activation remain elusive. Here, we tested the effect of γ-synuclein, a member of the synuclein family of proteins, on the activation of AKT. We show that the expression level of γ-synuclein is increased in non-small cell lung cancer (NSCLC) tissues. γ-Synuclein binds to the protein kinase domain of AKT and promotes its phosphorylation. Overexpression of γ-synuclein in H157 cells enhances cell proliferation and protects the cells from staurosporine-induced cytotoxicity. Knockdown of γ-synuclein attenuates AKT activation and cell proliferation induced by epidermal growth factor. The effect of γ-synuclein is abolished when AKT is depleted. Thus, γ-synuclein promotes cell survival and proliferation via activating AKT and may play a causal role in the pathogenesis of NSCLC.

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