Oligomer formation

Dtugs in clinical development that directly target the A(3 pathway are at an early stage. Inhibitors of (3- and y-secretases that can lower the A 3 production have entered clinical phase trials with (3-secretase inhibitors being years behind the development of y-secretase inhibitors. Functional y-secretase inhibitors have been shown to reduce the rate of A 3 formation in vitro and in vivo. The reduction of A 3 monomer levels could prevent oligomer formation and subsequent syn-aptotoxicity. Numerous anti-amyloid approaches to... 

In order to prove that intramolecular cyclization occurs before telechelic oligomer formation, an experiment similar to previous work by Calderonlf is performed using 14 in place of Calderon s classical catalyst system. Macrocyclic species are formed when a toluene solution of polybutadiene is exposed to this catalyst, supported by both NMR and GC data. The vinylic resonances are clearly shifted upfield from polybutadiene. GC analysis shows macrocyclic trimers and tetramer regioisomers. 

Ito, K., Hashizuka, Y., and Yamashita, Y., Equilibrium cyclic oligomer formation in the anionic polymerization of e-caprolactone, Macromolecules, 10, 821-824, 1977. 

Five-membered unsubstituted lactone, y-butyrolactone (y-BL), is not polymerized by conventional chemical catalysts. However, oligomer formation from y-BL was observed by using PPL or Pseudomonas sp. lipase as catalyst. Enzymatic polymerization of six-membered lactones, 8-VL and l,4-dioxan-2-one, was reported. 8-VL was polymerized by various lipases of different origins. The molecular weight of the enzymatically obtained polymer was relatively low (less than 2000). 

Techniques were developed for the dilute solution characterization of polydlchlorophosphazene. The purity of the trimer has a significant effect on oligomer formation, polymerization time and polymer MW and MWD. The polymers prepared in this study have high molecular weights and broad molecular weight distributions and probably have similar, if not identical, chain structures. 

Five-membered unsubstituted lactone, y-butyrolactone, is not polymerized by conventional chemical catalysts. On the other hand, oligomer formation from y-butyrolactone was observed by using PPL or Pseudomonas sp. lipase as catalyst [23,69]. 

Patel, R. C., Lange, D. C. and Patel, Y. C. (2002). Photobleaching fluorescence resonance energy transfer reveals ligand-induced oligomer formation of human somatostatin receptor subtypes. Methods 27, 340-8. 

Figure 1.24 A two-step protocol using a homobifunctional crosslinking agent offers more control than single-step methods, but still may result in oligomer formation.

The enantioface and also the configuration (s-trans, s-cis) of the prochiral butadienes involved in the several elementary steps are of crucial importance for the stereocontrol of the cyclo-oligomer formation. Oxidative coupling, for example, can occur between two cA-butadienes, two /rum-butadienes or between cis- and /nmv-butadiene with either the same or the opposite enantioface of the two butadienes involved. The several stereoisomers are exemplified for the [Ni°(butadiene)2L] active catalysts for cyclodimer formation, that are schematically depicted in Fig. 1, together with the related stereoisomers of the ry ri fC1) and bis(r 3) octadienediyl-Ni11 species 2a and 4a, respectively. For each of the individual elementary steps there are several stereochemical pathways, which are exemplified in Fig. 1 for the... 

Kinetics (oligomer formation and aging) Thermodynamic Sinks (non-stoichiometric molecules)... 

A typical flowchart for a chelate process is shown in Fig. 2.6.46 In this process, titanium isoproproxide is first added to zirconium butoxide. Acetic acid is then added to the precursor mixture for suppression of hydrolysis. Finally, lead acetate is then added to the solution, followed by the addition of alcohol and water for control of solution viscosity, solution stability, and oligomer formation.46... 

Scholze, P, Freissmuth, M., and Sitte, H. H. (2002) Mutations within an intramembrane leucine heptad repeat disrupt oligomer formation of the rat gaba transporter 1. J. Biol. Chem. 277,43682 13690. 

Patel, R. C Kumar, U Lamb, D. C., et al. (2002) Ligand binding to somatostatin receptors induces receptors-specific oligomer formation in live cells. Proc. Natl. Acad. Sci. USA 99, 3294-3299. 

Fukushima, Y., Asano, T., Satioh, T., et al. (1997) Oligomer formation of histamine H2 receptors expressed in Sf9 and COS7 cells. FEBS Lett. 409, 283-286. 

Schlunegger, M. P., Bennett, M. J., and Eisenberg, D. (1997). Oligomer formation by 3D domain swapping A model for protein assembly and misassembly. Adv. Protein Chem. 50, 61-122. 

Polyglycerols obtained by the dehydration of glycerol (Scheme 3.7) are employed as surfactants, lubricants, cosmetic, food additives, etc. Their esterification with fatty acids leads also to valuable emulsifiers or metal-working fluids. Zeolites have been used to take advantage of their shape selectivity effect to minimize oligomer formation, as described in two patents [61, 62]. A fair compromise between activity and selectivity has been obtained by Clacens et al. [63] using cesium-impregnated mesoporous MCM-41. 

Peebles et al. [50] found that the formation of cyclic oligomers at 290 °C increased with decreasing Mn of the polymer, and that the cyclization rate depended linearly on the hydroxyl end group concentration. Therefore, a backbiting mechanism (cyclodepolymerization) has been proposed as a probable mechanism for oligomer formation (Figure 2.9). 

Ha and Choun [51] confirmed these findings from the investigation of cyclic oligomer formation at 270 °C. They derived a rate equation for cyclic oligomer formation taking thermal degradation of the polymer into account. 

Peebles, L. H., Huffman, M. W. and Ablett, C. T., Isolation and identification of the linear and cyclic oligomers of polyethylene terephthalate) and the mechanism of cyclic oligomer formation, J. Polym. Set, PartA-1, 7, 479 (1969). 

Cephalosporins are mostly degraded via intramolecular aminolysis (see above, Fig. 5.8). However, high drug concentrations may also favor degradation via oligomer formation [119]. In the case of loracarbef (5.44, Fig. 5.16), which is not subject to intramolecular aminolysis, the formation of dimeric structures becomes predominant under moderately acidic conditions [120],... 

Fig. 5.15. The oligomer formation of a-aminopenicillins involves the intermolecular attack by the a-amino group on the /3-lactam ring [117]...

Krishnan-Ghosh, Y. Whimey, A. M. Balasubramanian, S. Dynamic covalent chemistry of self-templating PNA oligomers Formation of a bimolecular PNA quadruplex. Chem. Commun. 2005, 3068-3070. 

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