In humans, 5' m(7)G cap addition is accomplished cotranscriptionally by the sequential action of the capping enzyme (Hce1) and the cap methyltransferase (Hcm1). We found that guanylylation and methylation occur efficiently during transcription with t(1/2)'s of less than 15 and 70 s, respectively. A two to four order of magnitude increase was found in the rate of guanylylation of RNA in transcription complexes compared to free RNA. This stimulation required only the RNA polymerase II elongation complex and Hce1. Capping activity was weakly associated with elongation but not preinitiation complexes. The CTD was not required for functional coupling but stimulated the rate of capping 4-fold. Inhibition of Cdk7 but not Cdk9 similarly slowed the rate of capping.

Direct acyl radical formation of linear aldehydes (RCH2-CHO) and subsequent hydroacylation with electron-deficient olefins can be effected with various types of metal and nonmetal catalysts/reagents. In marked contrast, however, no successful reports on the use of branched aldehydes have been made thus far because of their strong tendency of generating alkyl radicals through the facile decarbonylation of acyl radicals. Here, use of a hypervalent iodine(III) catalyst under visible light photolysis allows a mild way of generating acyl radicals from various branched aldehydes, thereby giving the corresponding hydroacylated products almost exclusively. Another characteristic feature of this approach is the catalytic use of hypervalent iodine(III) reagent, which is a rare example on the generation of radicals in hypervalent iodine chemistry.

Scheme 2. Proposed pathway for the formation of iodanyl radical. Scheme 3. Oxidation of methyl valerate with 2 and 3 d.Scheme 4. Hypervalent iodine(III) reagents 3. [12] naph = naphthalene.

A strategy is described for modular catalyst development based upon metal-directed self-assembly of bifunctional subunits around a structural metal to form a heteroleptic complex in which a second set of ligating groups are now suitably disposed to bind a second metal to form a catalytic site. A library of chiral diphosphites was prepared via metal-directed self-assembly and used in a simple asymmetric allylic amination, giving enantiomeric excesses as high as 97%.

Asymmetric conjugate addition of α-heterosubstituted aldehydes such as α-amido and α-alkoxy aldehydes to vinyl sulfone was effected under the influence of structurally rigid trans-diamine-based Tf-amido organocatalyst (S,S)-2 with a dihydroanthracene framework to furnish α,α-dialkyl(amido)aldehydes and α,α-dialkyl(alkoxy)aldehydes with high enantioselectivity. The chiral efficiency of the structurally unique catalyst (S,S)-2 is apparent in comparison with (S,S)-1 and (S,S)-4 with similar functionality.

From a practical point of view, the development of a novel approach for the asymmetric synthesis of both enantiomeric products through catalytic asymmetric transformations with the same chiral catalyst would be very useful.[1] Various types of chiral metal complexes have already been introduced. [2] However, strictly speaking, many of these examples have employed a distinct three-dimensional association between a chiral ligand and different metals, or vice versa. In marked contrast, an initial effort for the synthetic application of chiral organocatalysts has appeared very recently, but has not been developed to a synthetically useful level. [3] In this context, we explored the capability of an additive to induce an unexpected inversion in catalyst selectivity for certain asymmetric transformations catalyzed by a single chiral organocatalyst. Herein we present the first practical example of such a system, employing achiral, organic acids as reliable additives in asymmetric, direct aldol reactions catalyzed by a chiral, cisdiamine-based, Tf-amido organocatalyst of type 1 (Tf = trifluoromethanesulfonyl Scheme 1). [4][5][6][7] Initally, the asymmetric direct aldol reaction of cyclohexanone and a-keto ester 3 a was carried out with organocatalyst 1 a to establish the optimum reaction conditions. The treatment of cyclohexanone 2 a and a-keto ester 3 a with 20 mol % of 1 a in methanol at 0 8C gave the corresponding aldol products 4 a in moderate yields; the major isomer, syn-4 a, was obtained with high enantioselectivity (Table 1, entry 1). We had previously observed a remarkable enhancement in enantioselectivity for the asymmetric conjugate addition of heterosubstituted aldehydes to vinyl sulfones by using bulky benzoic acid additives under the influence of a structurally rigid, trans-diamine-based, Tf-amide catalyst with a dihydroanthracene framework. [8] This finding prompted us to test a series of benzoic acid derivatives to probe their potential for the reversal of enantioselectivity in these products as well. [a]Entry Additive [b] Yield [c] [%] d.r. [d] (syn/anti) aldol ee [e] [%]

Zinc finger proteins comprise the largest class of eukaryotic transcription factors. The metal binding sites in these proteins have been proposed as plausible targets for exchange reactions between zinc and toxic metal ions that lead to the alteration of function of the proteins in gene transcription. According to the present work, both Cd 2+ and Pb 2+ displace Zn 2+ from transcription factor IIIA (TFIIIA). Neither product binds to the internal control region (ICR) of the 5 S rRNA gene, the normal binding site for Zn-TFIIIA. Furthermore, the adduct of Zn-TFIIIA with ICR is also reactive with Cd 2+ and Pb 2+ , leading to the dissociation of the DNA-protein complex. Cd-TFIIIA reacts with apometallothionein (apoMT) to form Cd-MT and apoTFIIIA. Similarly, Cd 2+ and Zn 2+ can be exchanged in the reaction of Cd-TFIIIA with Zn-MT. Zn-finger 3 of TFIIIA has also been examined to compare the reactivity of a single finger motif with fingers in the holoprotein. Zn-finger 3 reacts with much faster kinetics than the holoprotein. KeywordsZinc-finger; Cadmium; Lead TFIIIA; MetallothionienThe most common protein DNA binding motif among transcription factors in eucaryotes is the Zn finger structure that is stabilized through binding of a Zn 2+ ion to two imidazole nitrogen (N) and two cysteine sulfhydryl (S) ligands. In the absence of Zn 2+ its conformational integrity is lost and the domain no longer associates with DNA. Because transcription factors play such a central role in cell regulation, Zn finger proteins have attracted much attention.The prototypical Zn finger transcription factor is transcription factor IIIA (TFIIIA), isolated from the immature ovary of Xenopus laevis. It binds to the internal control region (ICR) of the 5 S ribosomal RNA gene and stimulates its transcription. The product 5 S rRNA competes with the ICR for binding Zn-TFIIIA to inhibit its own synthesis. TFIIIA largely comprises nine consecutive Zn finger domains which differentially interact with the ICR DNA or with 5 S rRNA.Studies with TFIIIA and other Zn finger structures suggest that the Zn 2+ is not bound as tightly in these molecules as in numerous other types of Zn-metalloproteins. Thus, when N 2 S 2 Zn finger proteins are prepared, buffers commonly contain Zn 2+ to insure that the isolated proteins are saturated with metal ion (Del Rio & Setzer, 1991 Titration data have been used to measure metal ion binding constants for F3. The results in Table 1 show that Zn 2+ does not bind strongly to F3, and both Cd 2+ and Pb 2+ display larger formations constants, indicating that these metal ions bind preferentially to F3 in comparison with Zn 2+ . Available information for two other finger peptides is also shown in Table 1. It is seen that there can be a large variation in binding affinity of Zn 2+ for related finger structures. In the case of CP1, peptide association with Zn 2+ is much more favorable than with Cd 2+ . These results show first that individual Zn finger sites will be differentially sensitive to the concentration of cellular Zn 2...

A practical approach to radical C-H bond functionalization by the photolysis of a hypervalent iodine(iii) reagent is presented. The photolysis of [bis(trifluoroacetoxy)iodo]benzene (PIFA) leads to the generation of trifluoroacetoxy radicals, which allows the smooth transformation of various alkylbenzenes to the corresponding benzyl ester compounds under mild reaction conditions.