Multimers

Before moving furtlier to tire multimer case we should outline one furtlier significant feature of a dimer. Dimer excited states have a well defined rotational strengtli [33, 34] ... 

With tlie development of femtosecond laser teclmology it has become possible to observe in resonance energy transfer some apparent manifestations of tire coupling between nuclear and electronic motions. For example in photosyntlietic preparations such as light-harvesting antennae and reaction centres [32, 46, 47 and 49] such observations are believed to result eitlier from oscillations between tire coupled excitonic levels of dimers (generally multimers), or tire nuclear motions of tire cliromophores. This is a subject tliat is still very much open to debate, and for extensive discussion we refer tire reader for example to [46, 47, 50, 51 and 55]. A simplified view of tire subject can nonetlieless be obtained from tire following semiclassical picture. 

Endonuclease-catalyzed hydrolysis of DNA at the internucleosomal linker regions into multimers of 180 base pairs which are visualized by electrophoresis as a ladder of nuclear DNA fragments. Access of the endonuclease to DNA is facilitated by depletion of polyamines, and the activity of the enzyme is mcrea.sed by and decreased by ADP-tibosylation. Thus, agents that increase intracellular Ca " or inhibit l>oly(ADP-ribose) polymerase can induce apoptosi.s. ... 

The terms polypeptide and protein are used interchangeably in discussing single polypeptide chains. The term protein broadly defines molecules composed of one or more polypeptide chains. Proteins having only one polypeptide chain are monomeric proteins. Proteins composed of more than one polypeptide chain are multimeric proteins. Multimeric proteins may contain only one kind of polypeptide, in which case they are homomultimeric, or they may be composed of several different kinds of polypeptide chains, in which instance they are heteromultimeric. Greek letters and subscripts are used to denote the polypeptide composition of multimeric proteins. Thus, an ag type protein is a dimer of identical polypeptide subunits, or a homodimer. Hemoglobin (Table 5.1) consists of four polypeptides of two different kinds it is an hetero-multimer. 

T. K. Nadler, S. K. Paliwal and F. E. Regnier, Rapid, automated, two-dimensional liigh-performance liquid cliromatographic analysis of immunoglobulin G and its multimers , 7. Chromatogr. A 676 331-335 (1994). 

Fig. 6-12. Different types of binding sites in polymers eontaining miero- (site B), meso- and maerop-ores (site A) C) Embedded site, D) Site eomplementary to dimer or multimer, E) Indueed binding site, E) Nonseleetive site, G) Residual template.

The ability of a solute to associate with itself can be expressed by the degree of association (/). The / is obtained by dividing the stoichiometric mole fraction of the solute by the effective mole fraction of the solute. Assuming that a single multimer species in equilibrium with a monomer is a dimer,/values range from 1.0 to 2.024). 

Collagen-like (ColQ) tailed forms or asymmetric multimers Characterized by triple helical structure of three collagenic subunits Q, each associated with... 

Sequence-specific transcription factors often bind as multimers especially as dimers to DNA. This allows binding of mirror-imaged sequences (palindromes) in the DNA that are separated by a few spacer nucleotides. The dimerization is stabilized by hydrophobic motifs within dimerization motifs of each transcription factor molecule. Dependent on the nature of the dimerization domain and the abundance of individual transcription factors homo- or heterodimers can form and bind to palindromes with differential activity. 

Another important issue is the size-limitation of AAV vectors the maximum size of rAAV genomes is 4.7 kb. To overcome this size constraint, dual vector systems with split-genomes have been developed [1] dual vectors are based on episomal circular multimers formed by the AAV vector genomes. However, the efficacy of the dual vector system has been questioned. 

HIV integrase consists of three distinct domains. The N-terminal domain contains a HHCC motif that coordinates a zinc atom that is required for viral cDNA integration. Three highly conserved amino acids (D,D-35-E) are embedded in the core domain, which form the acidic catalytic triad coordinating one or possibly two divalent metals (Mn + or Mg +). The C-terminal domain (residues 213-288) is responsible for unspecific DNA binding and adopts an overall SH3 fold (Chiu and Davies 2004). The enzyme functions as a multimer and to this end all three domains can form homodimers. 

Virus maturation and assembly at the cell membrane or the nuclear membrane has long been seen as a potential target for antiviral compounds. For the virus to mature and be released in a conformation that will insure stability and survival of the viral genome in the exttacellular enviromnent, the protein subunits of the capsid or nucle-ocapsids have to be transported to the assembly point where they will form the final particles around the viral nucleic acid. If this process does not occur in an orderly and programmed manner, the capsid subunits will not form the required multimers and the viral components will become targets for the cellular disposal mechanisms. 

The transferred proton is actually associated with a cluster of water molecules. Protons exist in solution not only as H30, but also as multimers such as H502 and... 

FIGURE 2.5 Schematic representation of hydrogen-bonded self-associative structures of higher fatty acids (a) cyclic associative dimer and (b) linear associative multimer. 

A 2B 2M 2N Type 3 vWD Decreased platelet-dependent vWF function owing to lack of larger multime rs Increased platelet-dependent vWF function owing to lack of larger multime rs Defective platelet-dependent vWF functions not associated with multimer defects Defective vWF binding to factor VIII Severe quantitative deficiency of vWF 1 %-5% Autosomal recessive... 

Rossotti and co-workers45 introduced the term "oligomers for dimers and even multimers or ra-mers in non-aqueous solutions real examples of such self-aggregates (non-hydrogen bonded) have been reported46 for quaternary ammonium thiocyanates, iodides and perchlorates with ra-mers with n even up to 20. 

The pJuFo system also has the potential to display homodimers or homomultimeric proteins on the surface of the phage. This is possible because the protein of interest is expressed independent of the phage proteins. Therefore, the Fos-ORF fusion protein is secreted to the periplasm, the Fos portion interacts with Jun to attach the protein to the phage, and other copies of the Fos-ORF protein can interact with each other to form a dimer or multimer. However, the successful display of homodimers has not been demonstrated in practice. 

The g-tensor principal values of radical cations were shown to be sensitive to the presence or absence of dimer- and multimer-stacked structures (Petrenko et al. 2005). If face-to-face dimer structures occur (see Scheme 9.7), then a large change occurs in the gyy component compared to the monomer structure. DFT calculations confirm this behavior and permitted an interpretation of the EPR measurements of the principal g-tensor components of the chlorophyll dimers with stacked structures like the P 00 special dimer pair cation radical and the P700 special dimer pair triplet radical in photosystem I. Thus dimers that occur for radical cations can be deduced by monitoring the gyy component. 

Wick T, Kaye N, Jensen W. Unusually large von Willebrand factor multimers increase adhesion of sickle erythrocytes to human endothelial cells under controlled flow. N Engl J Med 1982 337 1584-1590. 

Acetyl-CoA carboxylase (ACCase) carboxylates acetyl-CoA into malo-nyl-CoA and therefore represents the first committed step in fatty acid biosynthesis. ACCase is a multimer essential for cell growth whose components are highly conserved among bacteria, making it a promising broad-spectrum target [8]. 

Flumate-P (also contains high molecular weight multimers of von Willebrand factor)... 

A similar type of biotin-dendritic multimer also was used to boost sensitivity in DNA microarray detection by 100-fold over that obtainable using traditional avidin-biotin reagent systems (Stears, 2000 Striebel et al., 2004). With this system, a polyvalent biotin dendrimer is able to bind many labeled avidin or streptavidin molecules, which may carry enzymes or fluorescent probes for assay detection. In addition, if the biotinylated dendrimer and the streptavidin detection agent is added at the same time, then at the site of a captured analyte, the biotin-dendrimer conjugates can form huge multi-dendrimer complexes wherein avidin or streptavidin detection reagents bridge between more than one dendrimer. Thus, the use of multivalent biotin-dendrimers can become universal enhancers of DNA hybridization assays or immunoassay procedures. 

Gel-filtration analysis reveals bands of molecular mass 40-70 kDa. These represent dimers (and some multimers) of the IFN-y polypeptide. Its biologically active form appears to be a homodimer in which the two subunits are associated in an antiparallel manner. 

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