Aggregation of proteins

Aggregation of proteins is a microscopic process of protein molecule association. The aggregates may be dimers or larger oligomers that remain in solution, yet may alfect the observed biological activity. Precipitation refers to the formation of visible proteinaceous particles, which may reduce potency in addition to altering the appearance of a formulation and its performance in various infusion devices. 

H. R. Costantino, R. Langer, and A. M. Klibanov, Solid-phase aggregation of proteins under pharmaceutically relevant conditions, J. Pharm. Sci., 83, 1662 (1994). 

Jaenicke, R. (1995). Folding and association versus misfolding and aggregation of proteins. Philos. Trans. R. Soc. Lond. B Biol. Sci. 348, 97-105. 

Perutz, M. F., Pope, B. J., Owen, D., Wanker, E. E., and Scherzinger, E. (2002b). Aggregation of proteins with expanded glutamine and alanine repeats of the glutamine-rich and asparagine-rich domains of Sup35 and of the amyloid /1-peptide of amyloid plaques. Proc. Natl. Acad. Sci. USA 99, 5596-5600. 

Aggregation of proteins into oligo- and poly-globular complexes. In this case the opposite situation will occur, i.e., a shift of the density of bands towards the high-molecular weight zone (start). 

From the data presented it can be concluded that the processes of both destruction and aggregation of proteins do not contribute significantly to the photodynamic treatment. 

Small amounts of surfactants may be used to prevent aggregation of proteins and may enhance the refolding process when the dried protein dissolves. Buffers may also help to prevent aggregation of the dissolved drug. Similarly, polymers may be used as aggregation inhibitors or to form matrices. Chan et al. [86] prepared crystalline powders of recombinant human deoxyribonuclease with high fractions of sodium chloride. These powders were formulated as adhesive mixtures on lactose and mannitol and showed improved aerosolization behaviour compared to the pure protein. 

Chromatographic Analysis. The samples of native and ozonized lysozyme (lysozyme treated with ozone just to the point of complete inactivation) were analyzed by column chromatography. The column (0.8 X 56 cm.) containing DEAE-Sephadex A-50 (Cl form) resin, was equilibrated with 0.1 M Tris Cl buffer, pH 8.3, and loaded with about 2-U mg of protein. Aliquots eluted with 0.1 M Tris-Cl pH 8.3 were collected and absorbance at 278 nm was measured. The native lysoz3mie eluted earlier than the ozonized products. This difference may be assoicated with both aggregation of protein and ionic behavior of the residues. 

B) aggregates of protein nanofibres bridged by bioactive species... 

Jones LS, Kaufmann A, Middaugh CR. Silicone oil induced aggregation of proteins. J Pharm Sci 2005 94(4) 918-927. 

Proteins of egg white denature more rapidly than those of whey protein concentrate (13, 34). However, isolated p-lactoglobulin from the whey concentrate was more susceptible to surface denaturation than egg white ovalbumin. These data suggest that whey contains substances that protect the proteins from surface denaturation and may account for the lower stability of whey protein concentrate foams than those of egg white protein. A balance between the disaggregation effect of select pH values and the tendency toward greater aggregation of proteins at higher heating temperatures were correlated closely with maximum foam stability (13, 15). 

Enzymatic modification of proteins applicable to foods is reviewed by Whitaker ( ). Described briefly are present uses of proteolytic enzymes for modifying proteins through partial hydrolysis. Major emphasis is placed on those enzymes which bring about aggregation of proteins, cross-link formation, and side chain modification through post-translational changes in the polypeptide chain. 

Despite some conflicting evidence (Kinsella and Fox, 1986), it appears that denaturation has little influence on the amount of water bound by whey proteins. However, other factors which may accompany denaturation (e.g. Maillard browning, association or aggregation of proteins) may alter protein sorption behaviour. Drying technique affects the water sorption characteristics of WPC. Freeze-dried and spray-dried WPC preparations bind more water at the monolayer level than do roller-, air- or vacuum-dried samples, apparently due to larger surface areas in the former. As discussed above, temperature also influences water sorption by whey protein preparations. The sorption isotherm for /Mactoglobulin is typical of many globular proteins. 

To some individuals, especially those who recall their experiences in organic chemistry laboratory, the ultimate step in purification of a molecule is crystallization. The desire to obtain crystalline protein has long been strong and many proteins have been crystallized. However, there is a common misconception that the ability to form crystals of a protein ensures that the protein is homogeneous. For many reasons (entrapment of contaminants within crystals, aggregation of protein molecules, etc.), the ability to crystallize a protein should not be used as a criterion of purity. The interest in pro-... 

Alternative Theories on How Hemoglobins and Other Allosteric Proteins Work Muscle Is an Aggregate of Proteins Involved in Contraction... 

Another useful physical property of the crystal is its density, which can be used to determine several useful microscopic properties, including the protein molecular weight, the proteinlwater ratio in the crystal, and the number of protein molecules in each asymmetric unit (defined later). Molecular weights from crystal density are more accurate than those from electrophoresis or most other methods (except mass spectrometry) and are not affected by dissociation or aggregation of protein molecules. The proteinlwater ratio is used to clarify electron-density maps prior to interpretation (Chapter 7). If the unit cell is symmetric (Chapter 4), it can be subdivided into two or more equivalent parts called asymmetric units (the simplest unit cell contains, or in fact is, one asymmetric unit). For interpreting electron-density maps, it is helpful to know the number of protein molecules per asymmetric unit. 

To reduce changes of the active constituent during storage (e.g. unfolding or aggregation of proteins. 

Fig. 1 UV/vis absorption spectra following the aggregation of protein A coated gold nanoparticles in the presence of antiprotein A for a the control—prior to adding antiprotein A, b at 30 min, and c at 60 min. The solution contained 7.8 x 1011 gold nanoparticles/mL and 0.32 ixg/mL antiprotein A in phosphate-buffered solution at pH 7.0...

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