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Temperature: high temperature accelerate oxidation, reduction and hydrolysis reaction which lead to drug degradation 2. pH: • Acidic and alkaline pH influence the rate of decomposition of most drugs. The growth rate has been shown to decrease or increase, or be independent of peptide concentration, depending upon the peptide/conditions and rate-limiting step. Area of base of support, ie a wider base of support means more stability.. Musculo-skeletal system – Eg muscle attachment to bones and formation of joints allows movements into stable positions. At pH 8.0 there is a strong dependence on ionic strength due to Debye screening and increasing ionic strength accelerates aggregation by up to a factor of ten. This process can be induced by a solid–water (surface), or water–air interface or occur in solution. The stability of joints is a topic of great clinical importance; it explains why some joints are more prone to dislocation and injury than others. This occurs because many investors are willing to buy the stock at higher and … iii, sec. Trait theory in cross-cultural use. KinTek is used, see Model 3 in . Flow as a factor is about emotion, stability, durability, evolution, and emotional immersion. We are grateful to many scientists in the protein and peptide aggregation field for interesting discussions. Google Scholar In the West the anti-communist solidarity of North and South America and the North Atlantic Treaty are apparently part of the same trend toward consolidation. Amino acids such as methionine, cysteine, histidine, tyrosine and tryptophan in peptides are susceptible to oxidation under some conditions encountered during pharmaceutical development. Elongation of the nucleus is rapid relative to its formation giving rise to the sigmoidal aggregation kinetics often observed (figure 5a). (a) Amorphous aggregates of 300 µM GLP-1 in water formed after incubation at room temperature for one week. Slope stability refers to the condition that an inclined slope can withstand its own weight and external forces without experiencing displacement. 2. In peptides, an Asn-Gly sequence is particularly prone to deamidation and is considered a ‘hot spot’ of reactivity. The most commonly used preservatives in pharmaceutical development are m-cresol, phenol and benzyl alcohol. Stability is the ability of an object to maintain its balance after being disturbed. Many studies have confirmed that the rate of peptide and protein adsorption is normally governed by diffusion, and is thus a function of concentration . The e-mail addresses that you supply to use this service will not be used for any other purpose without your consent. Alternatively, a fibril can fragment to create two shorter fibrils thus increasing the number of nuclei and therefore elongation/growth sites (bottom). This includes the incorporation of non-natural amino acids , engineering of disulfide bonds [133–137] and lipidation or acylation of the peptide [138,139]. However, the fact that these peptides are frequently used at high concentrations and are required to have long-term physical stability under these conditions makes the problem particularly acute. Asp degradation is similar to Asn degradation resulting in the formation of iso-Asp and racemic products. Amorphous aggregates, also known as disordered aggregates, are unstructured and there are no ordered intermolecular interactions . (Newton’s First Law)States of Equilibrium As already discussed, pH strongly influences peptide stability and the potential for biomolecular aggregation. (f) Fibrils of 150 µM GLP-1 in 25 mM Tris, pH 8.5 formed after incubation for 144 h at 37°C, and then diluted 10-fold in ddH2O prior to imaging. Lowering of interfacial tension will result in lowering of interfacial energy, thus increasing the stability of emulsion. In this mechanism, a number of on-pathway oligomers may be formed prior to the nucleus. Many different studies on the dependence of amyloid formation on ionic strength over the past 10 years have shown that ions can influence both the kinetics of aggregation and the structure of fibrils formed. (Online version in colour. The factors that influence the stability of emulsion include the lowering of interfacial energy and the strength of interfacial film. It has been demonstrated that any interface (between solid, liquid or air) will affect the ability of water molecules to form a dynamic hydrogen-bonding network as in bulk water, and therefore air–water and ice–water interfaces are described in the literature as hydrophobic interfaces, because these interfaces do not allow hydrogen bonding . In addition, the side chain of Trp is known to undergo hydrolysis and the primary degradation product is called kynurenine [105,109]. Aggregates can be amorphous  or highly structured, e.g. Trait theory … Members of _ can log in with their society credentials below, First Published Online: September 6, 2016. Physical Education (A-Level Revision) Motion and Mechanics; Centre of Mass; Title . Another study shows that in the absence of impurities, amylin 20–29 does not spontaneously aggregate and is not amyloidogenic. In this case, the monomeric starting material is converted into oligomers, and ultimately a species that can act as a nucleus for rapid fibril growth. This includes aromatic amino acids His, Trp and Tyr and sulfur-containing side chains Met and Cys [105,109,111]. See  for an excellent review on atomic resolution structures of amyloid fibrils. In addition, small amounts of deamidated material can induce amyloid formation of the purified peptide. Unfortunately, there are few reports about the impact of degradation impurities and counter ion salts on the kinetics of peptide aggregation and there is a lack of information about the influence of other common impurities in synthetic peptides on either the mechanism or the kinetics of aggregation. How these kinetic parameters depend upon peptide concentration has been established for many systems, including Aβ , α-synuclein , tau , glucagon-like peptide-1 (GLP-1)  and other peptides. A number of polymers have been shown to stabilize drug products including PEGs. Many intrinsic and extrinsic factors affect the conformational equilibria (β-strand shown as a green arrow, α-helix shown as a red cylinder), including chemical degradation/modifications (shown as a purple circle). One contribution of 12 to a theme issue ‘Self-assembled peptides: from nanostructures to bioactivity’. Recently, some excellent reviews on biologics formulation [215,216] and excipients, including protein–excipients interactions [191,216,217] have been published. The techniques used for analyzing static positions of the body are only approximate inasmuch as forces accompanying movement incorporate such dynamic factors as acceleration, momentum, friction, the changing positions of rotational axes, and the resistance and support offered by tissues other than muscles. The growth rate is also dependent upon secondary nucleation steps, if they exist, such as fragmentation of the fibrils to form small fibrils with a net increase in reactive fibril ends on which growth can occur, or secondary nucleation sites on the surface of a fibril (figure 4a) .
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