Cleavage, multifunctional

Auldridge, M. E., A. Block et al. (2006). Characterization of three members of the arabidopsis carotenoid cleavage dioxygenase family demonstrates the divergent roles of this multifunctional enzyme family. Plant J. 45(6) 982-993. 

Triazenes are disguised diazonium ions which can be released under very mild acidic conditions. Inspired by the use of triazenes in natural product synthesis by Nicolaou et al. [127] and the pioneering work of Moore et al. [128, 129] and Tour et al. [130] in the synthesis of triazenes on a solid support and the final detachment to give iodoarenes, a whole set of triazene-based linkers has been developed (Tab. 3.10) [131]. The arene diazonium salts generated from the triazene linkers offer diverse opportunities for multifunctional cleavage. Two linkers based on tria-... 

Nowadays, solid-phase synthesis has been used as a powerful tool in organic chemistry, especially to prepare small molecule libraries. New linkers to obtain different functionalities after cleavage have been developed. There are different linkers strategies (Fig. 3.2), for example traceless linkers, multifunctional linkers, safety catch linkers, fragmentation/ cycloreversion cleavage linkers, cyclization cleavage linkers, which are useful methods for combinatorial solid-phase chemistry. 

In contrast to traceless cleavage, which releases only hydrocarbon-like molecules, multifunctional cleavage provides additional diversity of functional compounds in... 

Examples for multifunctional cleavage are given by the use of sulfone-, silyl- or triazene-linkers [202]. Wagner et al. for example used a cleavage Suzuki reaction on a sulfonium-linker (105) (Scheme 3.8) [206]. 

Use has been made of the bond cleavage processes initiated by an adjacent carbonyl function for the modification of steroidial ketols such as 18 [97], Reduction in ethanol eliminates the hydroxyl function and in the same reaction, the carbonyl function is reduced to a secondary alcohol. In compound 19 where there are several groups to act as electrophores, carbon-oxygen bond cleavage is initiated from the most easily reduced dienone function [98], Cleavage of the carbon-oxygen bond in an a-acetoxycarbonyl function is achievable in good yields from multifunctional compounds such as the sesquiterpene taxol [99]. 

Electron beam irradiation is one of the methods of cross-linking in fhis process. The other methods use peroxide, multifunctional azide, or an organofunctional silane. Polyethylene resins respond to electron beam irradiation well since the rate of cross-linking exceeds significanfly fhe chain scission. Polypropylene (PP) is prone to P-cleavage, which makes if difficult to cross-link by a free radical process. For fhaf reason, PP resins... 

Calixcrown 5, featuring two diethylaminomethyl side-arms at the polyether bridge, testifies an attempt at a higher order multifunctional catalysis of ester cleavage, namely, from nucleophilic-electrophilic to nucleophilic-electrophilic-general acid catalysis [20]. 

In higher animals as well as in My cobacterium,207 yeast,208 and Euglena, the fatty acid synthase consists of only one or two multifunctional proteins. The synthase from animal tissues has seven catalytic activities in a single 263-kDa 2500-residue protein 209 The protein consists of a series of domains that contain the various catalytic activities needed for the entire synthetic sequence. One domain contains an ACP-like site with a bound 4 -phosphopantetheine as well as a cysteine side chain in the second acylation site. This synthase produces free fatty acids, principally the C16 palmitate. The final step is cleavage of the acyl-CoA by a thioesterase, one of the seven enzymatic activities of the synthase. See Chapter 21 for further discussion. 

RNA phosphodiesler backbone, they have also been shown lo participate in cleavage of DNA. replication of RNA, and reactions with phosphate monocstcrs, Other RNAs arc associated with enzymes to form riboprotein complexes involved iit many biological processes. The multifunctional character of RNA, particularly the involvement of RNA ill enzymatic processes, has led to the hypothesis that life on earth evolved from RNA. and that RNA had both the genetic and catalytic functions commonly associated with DNA and proteins, respectively. 

One limitation of monofunctional linkers is that they provide only one type of compound in a library. However, the so-called multifunctional linkers offer the important opportunity to incorporate additional diversity upon cleavage. In this case, the number of new functionalities (Fig. 1, type I) can multiply the number of compounds produced (Fig. 2). 

Fig. 2. Diversity through multifunctional cleavage. (See color insert.)...

Thrombin is a multifunctional serine protease involved in the cleavage of fibrinogen to fibrin and in the activation of a variety of cell types, including platelets and endothelial cells (17),... 

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