Oligomeric complexes

The first step follows a modification of the well known procedure of Krej-carek and Tucker [38] yielding the monomethylamide of DTPA 27. After dehydration with glacial acetic acid the monomethylimide 28 has been obtained as an activated polycarboxylate compound. Subsequent reaction with 1,3-diaminopropane yielded the DTPA-mono(methyl-propylamino)amide Hydro-choride 29. The reaction of 29 with 28 afforded the dimeric ligand 30. 

Starting with the tetraethyl ester of DOTA the potassium salt of the triester 31 has been obtained by a partial saponification. To the solution of this compound in anhydrous tetrahydrofuran dicyclohexylcarbodiimide and 1-hydroxybenzo-triazole has been added followed by tris(2-aminoethyl)amine. Subsequent hydrolysis of the ester groups yielded the nonaacid 32. 

Neutral bis-and tris-gadolinium complexes of the oligomeric ligands have been obtained in the usual manner with gadolinium oxide and the corresponding dysprosium complexes by reaction with dysprosium oxide The latter might be useful as X-ray contrast agents. 

In recent years a multitude of oligomeric lanthanide complexes has been published [39-41]. 

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Ca2+ Channel Blockers. Figure 1 Most voltage-gated Ca2+ channels exist as a hetero-oligomeric complex of several subunits, a 1 subunits form the Ca2+-selective ion pore and contain the voltage-sensors of the channel. 

In chronic myelogenous leukemia (CML) as well as in a subset of acute lymphoblastic leukemia (ALL) Bcr-Abl, a fusion protein of c-Abl and the breakpoint cluster region (bcr), is expressed in the cytosol of leukemic cells. This fusion protein forms homo-oligomeric complexes that display elevated kinase activity and is the causative molecular abnormality in CML and certain ALL. The transforming effect of Bcr-Abl is mediated by numerous downstream signaling pathways, including protein kinase C (PKC), Ras-Raf-ERK MAPK, JAK-STAT (see below), and PI3-kinase pathways. 

HVA calcium channels are biochemically hetero-oligomeric complexes of five proteins encoded by four gene families (Fig. 1) The ax subunits of 190-250 kDa contain the voltage-sensor, the selectivity filter, the ion-conducting pore, the binding sites for most calcium... 

The functional groups outlined in Fig. 10 are all bifunctional ligands that can, at least from a theoretical point of view, form monomeric, dimeric, or oligomeric complexes with metal ions or a diorganoboryl group. 

Faye, A., Esnous, C., Price, N.T., Onfray, M.A., Girard, J., and Prip-Buus, C. (2007) Rat liver carnitine palmitoyltransferase 1 forms an oligomeric complex within the outer mitochondrial membrane.. Biol. Cbem. 10.1074/jbc.M705418200. 

Cheng, Z. J. and Miller, L. J. (2001) Agonist-dependent dissociation of oligomeric complexes of G protein-coupled cholecystokinin receptors demonstrated in living cells using bioluminescence resonance energy transfer. J. Biol. Chem. 276,48040-48047. 

Yesilaltay, A. and Jenness, D. D. (2000) Homo-oligomeric complexes of the yeast alpha-factor pheromone receptor are functional units of endocytosis. Mol. Biol. Cell. 11,2873-2884. 

In addition to the dimer bands higher oligomeric complexes were obtained by cross-linking chromatin. 

Davis et al. [66] developed an oligo(cyclooctene)-supported Co-OAc salen complex 25 (Figure 9) which efficiently catalyzed HKR of epichlorohydrin. The catalyst was recycled many times with negligible deactivation. The oligomeric complex was found to be 25 times more reactive than monomeric Co-salen. This study also gives possible modes of deactivation of Jacobsen s Co-salen catalyst during HKR of epichlorohydrin by spectroscopy, combined with recycling studies. 

The characteristics of the ubiquitination cascade suggest that the substrate specificity of file ubiquitin system may be extended through association of a limited number of E2 and 3 enzymes into multiple oligomeric complexes (Hochstrasser, 1996). 

A primary function of the SH3 domains is to form fimctional oligomeric complexes at defined subcellular sites, frequently in cooperation with other modular domains. SH3 domains are foimd in many proteins associated with the cytoskeleton or with the plasma membrane. Examples are the actin binding protein a-spectrin and myosin lb. Furthermore, SH3 interactions are involved in signal transduction in the Ras pathway (see Chapter 9). 

It is assumed that the Jak kinases bind to a cytoplasmic section of the receptor, which is in the vicinity of the membrane and contains two conserved sequence elements, Box 1 and Box 2. Binding of the Jak kinases leads to their activation, a process linked to mutual phosphorylation of the Jak kinases (Fig. 11.6). Activation of the Jak kinases may take place in a homodimeric receptor complex or it may also occm in hetero-oligomeric complexes. The circumstances are comphcated in that two (or more) Jak kinases may associate at an activated receptor. Two different Jak kinases are required for signal transduction via interferon receptors (see Fig. 11.8). Furthermore, the different Jak kinases are specific for the corresponding receptors. 

In total, TGPP-Smad signal conduction has distinct similarities to signal conduction in the Jak-Stat pathway (see 11.1.3). In both pathways, cytosolic transcription factors are activated by phosphorylation and are translocated in oligomeric complexes to the nucleus and the DNA. Common to both pathways is the short distance from the extracellular signal to the transcription level. 

Various members of the Bcl-2 family can interact with another via the BH domains and form hetero-oligomeric complexes in which the different activities neutralize one another. The relationship of proapoptotic and antiapoptotic Bcl-2 family proteins thus helps to determine a cell s susceptibility to apoptosis. 

Haslekas C, Breen K, Pedersen KW et al. The inhibitory effect of ErbB2 on epidermal growth factor-induced formation of clathrin-coated pits correlates with retention of epidermal growth factor receptor-ErbB2 oligomeric complexes at the plasma membrane. Mol Biol Cell 2005 16 5832-5842. 

Other oligomeric complexes are obtained with nitrogen donor ligands including amides, such as [Au4 NSiMe3)3 4] [226], or formamidates such as [Au4 (NPh)2CH 4] [227], triazenides, such as [Au4 (NPh)2N 4] [228], or pyrazolates, such as the trinuclear species commented above or the hexanuclear [Au6(2-5-Ph2pz)6] [229]. 

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