Retrograde fragmentation

Scheme 3.10. Retrograde fragmentation during the synthesis of (+)-Avermectin Bio...

Scheme 3.12. Alternative sequence as a solution to retrograde fragmentation.

In all likelihood, conditions such as Na(Hg)/MeOH would generate a certain amount of alkoxide 128, and an equilibrium involving retrograde fragmentation leading to 126 and 95 could then take place [26-28]. Considering the accepted mechanism outlined in Scheme 3.24, other reasons can be invoked to explain the low efficiency of the reduction. 

A second example of a toxin that has been used as targeting device is tetanus toxin. Tetanus toxin is a potent neurotoxin, which can undergo uptake in the nerve endings of motor neurones and subsequent retrograde transport into the central nervous system. The nontoxic C-fragment of tetanus toxin (TTC,451 amino acids), has been used to increase the neuronal uptake of the therapeutic protein SOD [57]. Following intravenous infusion, the recombinant hybrid protein reduced the occurrence of ischaemia-induced cerebral infarction in rats [58]. 

The absolute neurospecificity of clostridial neurotoxins, and the ability of TeNT to undergo axonal retrograde transport, make them ideal tools to study endocyto-sis and sorting at the synapse, and of retro-axonal transport both in vitro and in vivo (reviewed in Deinhardt and Schiavo 2005). These processes, which are still poorly understood at the molecular level, represent an exciting area of application for clostridial neurotoxins and their binding fragments. 

Cabot JB, MennoneA, Bogan N etal. (1991) Retrograde, trans-synaptic and transneuronal transport of fragment C of tetanus toxin by synpathetic preganglionic neurons. Neuroscience. 40 805-23. 

Manning KA, Erichsen JT, Evinger C (1990) Retrograde transneuronal transport properties of fragment C of tetanus toxin. Neuroscience. 34 251 -63... 

Controlled free-radical polymerization (CFRP) has been used successfully to produce block, graft, and other controlled architecture copolymers within the last decade for a variety of free radically polymerizable monomers. The main techniques include reversible addition fragmentation and transfer (RAFT) polymerization, stable free-radical polymerization (SFRP) mediated by nitroxide/alkoxyamine based radicals, atom transfer radical polymerization (ATRP), diphenyl ethylene (DPE) mediated polymerization, and novel precipitation/emulsion polymerization based methods like free-radical retrograde precipitation polymerization (FRRPP). ... 

Johannes, L., Tenza, D., Antony, C, and Goud, B. (1997). Retrograde transport of KDEL-bearing B-fragment of Shiga toxin. J. BioL Chem. 272,19554—19561. 

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