ARCAs

Indicates an apparent high degree of usefulness for SARA Pille III (i.c., includes two or more principal arca.s of use identified on page 12). 

It IS the stantng material for the preparation of nearly all manganese chemicals and is used m tenilizers tn arca.s of the world where there is a deficiency of Mn in the soil, since Mn is an essential irace element in plani growth. The anhydrous salt has a surprising Ihermal siabiliiy it remains unchanged even at red heal, whereas the solfates of Fe , Co" and Ni" all decompose under these conditions. 

MI2 J.LehmannandU.Hartmarm,ArcA.PAarm.(WsinAe/m)322,451 (1989). 

The first set of experiments was conducted in methanol. The substrate concentration was varied from 15 to 50 mM at a 200 pM concentration of 1 for the determination of kinetic parameters for the transformation of 8 into 9. The catalytic rate constant was determined to be 0.04 min and the Michael constant was determined to be 40 mM at 30°C. The rate constant is comparable to those reported for other dinuclear Cu(ll) complexes with a comparable Cu -Cu distance of 3.5 A, but about one magnitude lower than those observed for complexes with a shorter intermetallic distances (12-14), e.g. 2.9 A (kcat = 0.21 min ) (12) or 3.075 A (kcat = 0.32 min (13). The rate constant Aion for the spontaneous (imcatalyzed) oxidation of 8 into 9 was determined to be 6 x 10" min and corresponds to the oxidation without catalyst under otherwise identical conditions. The rate acceleration (Arca/Aion) deduced from these values is 60,000-fold. 

Synthesis of Anti-Reverse Cap Analogs (ARCAs) and their... 

Properties of ARCAs and ARCA-Capped mRNAs in Cell-Free... 

Properties of ARCA-Capped mRNAs in Mammalian Cells 221... 

Synthesis of ARCAs containing conventional phosphate chains 207... 

Stability of ARCA-capped mRNAs in cultured mammalian cells 224... 

This chapter briefly describes the general methodology for making both series of ARCAs and describes in detail the synthesis of two representative compounds P1-guanosine-5/ P3-(7,3/-0-dimethylguanosine-5/) triphosphate (Fig. 11.1, compound 2) and P1-guanosine-5/ P3-(7,3/-0-dimethyl-guanosine-5 ) /by- methylene-triphosphate (Fig. 11.1, compound 5). 

Figure ll.l Structures of ARCAs. Denotatious to Figure 11.1 Synthesis described in Jemielity etal. (2003) bSynthesis described in Kalek etal. (2006) cSynthesis described in Stepinski etal. (2001)...

The biophysical and biochemical characterization of ten ARCAs (Fig. 11.1, compounds 1-10) is presented. 

ARCAs are incorporated into RNA exclusively in the correct orientation to an extent that is similar to the standard cap (see previously), which makes them potentially useful compounds in terms of increasing translational efficiency when incorporated into RNA. Similarly, they should be effective for inhibiting protein synthesis as free analogs. To test the influence of the ARCAs on protein synthesis in vitro, we use the microccocal nuclease treated rabbit reticulocyte lysate system (RRL system) optimized for cap-dependent translation (Cai et al., 1999). Highly cap-dependent translation is achieved at 100 mM potassium acetate and 1.4 mM magnesium chloride. 

---