Excited states of free base chlorin (FBC), free base Bacteriochlorin (FBBC), pheophytin a (Pheo a), and chlorophyll a (Chlo a), which are derivatives of free base porphine (FBP), were calculated by the SAC (symmetry adapted cluster)/SAC-CI (configuration interaction) method. The results reproduced well the experimentally determined excitation energies. The reduction of the outer double bonds in the porphine ring in the order of FBP, FBC, and FBBC causes a breakdown of the symmetry and a narrowing of the HOMO-LUMO gap, which result in a red shift of the Q x band and an increase of its intensity. In the change from Pheo a to Chlo a, the Mg coordination reduces the quasidegeneracy in the Q x state and then increases the spectral intensity. The disappearance of the Q y humps from the absorption spectrum of Pheo a, compared with that of Chlo a, is due to the red shift of the Q y state.

The 2-5A system is one of the major pathways for antiviral and antitumor functions that can be induced by interferons (IFNs). The 2-5A system is modulated by 5-triphosphorylated, 2,5-phosphodiester-linked oligoadenylates (2-5A), which are synthesized by 2,5-oligoadenylate synthetases (2,5-OASs), inactivated by 5-phosphatase and completely degraded by 2-phosphodiesterase (2-PDE). Generated 2-5A activates 2-5A-dependent endoribonuclease, RNase L, which induces RNA degradation in cells and finally apoptosis. Although 2,5-OASs and RNase L have been molecularly cloned and studied well, the identification of 2-PDE has remained elusive. Here, we describe the first identification of 2-PDE, the third key enzyme of the 2-5A system. We found a putative 2-PDE band on SDS-PAGE by successive six-step chromatographies from ammonium sulfate precipitates of bovine liver and identified a partial amino acid sequence of the human 2-PDE by mass spectrometry. Based on the full-length sequence of the human 2-PDE obtained by in silico expressed sequence tag assembly, the gene was cloned by reverse transcription-PCR. The recombinant human 2-PDE expressed in mammalian cells certainly cleaved the 2,5-phosphodiester bond of 2-5A trimer and 2-5A analogs. Because no sequences with high homology to this human 2-PDE were found, the human 2-PDE was considered to be a unique enzyme without isoform. Suppression of 2-PDE by a small interfering RNA and a 2-PDE inhibitor resulted in significant reduction of viral replication, whereas overexpression of 2-PDE protected cells from IFN-induced antiproliferative activity. These observations identify 2-PDE as a key regulator of the 2-5A system and as a potential novel target for antiviral and antitumor treatments.

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