Protein aggregates, insoluble, formation

Fig. 9 Formation of protein aggregates. Proteins are oxidized due to environmental and metabolic influences. The part of the oxidized proteins escaping degradation form initial aggregates. These become cross-linked and insoluble due to intramolecular reactions. The chemically highly reactive surface of the aggregates tends to attract more proteins, in particular oxidized ones, and a process of enlarging of the aggregates takes place. It is important to note that these aggregates disturb cellular metabolism...

The use of . coli as an expression system is limited to those proteins where post-transla-tional modification such as the glycosylation or galactosylation of antibody fragments is not required. Inclusion body formation can be another disadvantage that occurs with this prokaryotic model, as these insoluble protein aggregates demand laborious and cost-intensive in vitro refolding (denatura-tion and renaturation) and purification steps. 

Amyloid-forming proteins, mainly in native state a-helical proteins undergoing a-helix to /1-strand conversion before or during fibril formation. Partially unfolded or misfolded /1-sheet fragments are discussed as precursors of amyloids. Protein aggregation combined with other events leads to the deposition of insoluble protein... 

After rehydration, the spectra of both samples are very native-like, indicating that the majority of nonnative molecules have refolded (Figure 3). However, in the spectrum of the sample lyophilized without sucrose, the appearance of a new band near 1625 cm", which is assignable to intermolecular j6-sheet structure, and the decreased intensities in vibrational bands ascribed to a-helix (1656 cm" ) and turn (1688-1665 cm" ) structures, indicate the formation of protein aggregates upon rehydration (see [11] for a detailed review of the study of protein aggregation with infrared spectroscopy). In this sample, 18% of the protein formed insoluble aggregates. In contrast, in the sample lyophilized with sucrose, only 9% insoluble aggregate was noted after rehydration. This reduction in... 

Though some cosmetic features of protein hydrolysates can be improved with increasing hydrophobicity (foaming, surfactant binding capacity), highly hydrophobic peptides are generally less water soluble and easily form insoluble aggregates with formation of... 

To prevent insolubility resulting from uncontrolled aggregation of extended strands, two adjacent parallel or antiparallel yS-peptide strands can be connected with an appropriate turn segment to form a hairpin. The / -hairpin motif is a functionally important secondary structural element in proteins which has also been used extensively to form stable and soluble a-peptide y9-sheet arrangements in model systems (for reviews, see [1, 4, 5] and references therein). The need for stable turns that can bring the peptide strands into a defined orientation is thus a prerequisite for hairpin formation. For example, type F or II" turns formed by D-Pro-Gly and Asn-Gly dipeptide sequences have been found to promote tight a-pep-tide hairpin folding in aqueous solution. Similarly, various connectors have been... 

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