Self physiological conditions

A few other aldehydes have been used in the reaction, either under normal or pseudo-physiological conditions. Of these, glycolalde-hyde, 5-hydroxypentanal, phenylacetaldehyde, and benzalde-hyde condense readily, but hydroxy and methoxy derivatives of these aromatic aldehydes give the product in poor yield,presumably due to their instability, as evidenced by their tendency to undergo self-condensation in acid solution. Reaction with phthaldehydic acids, such as opianic acid, proceeded readily, whereas reaction with chloral did not occur,... 

The first elastomeric protein is elastin, this structural protein is one of the main components of the extracellular matrix, which provides stmctural integrity to the tissues and organs of the body. This highly crosslinked and therefore insoluble protein is the essential element of elastic fibers, which induce elasticity to tissue of lung, skin, and arteries. In these fibers, elastin forms the internal core, which is interspersed with microfibrils [1,2]. Not only this biopolymer but also its precursor material, tropoelastin, have inspired materials scientists for many years. The most interesting characteristic of the precursor is its ability to self-assemble under physiological conditions, thereby demonstrating a lower critical solution temperature (LCST) behavior. This specific property has led to the development of a new class of synthetic polypeptides that mimic elastin in its composition and are therefore also known as elastin-like polypeptides (ELPs). 

We also wanted to evaluate the disassembly of our dendritic system under physiological conditions. Thus, we synthesized a self-immolative AB6 dendron 32 with water-soluble tryptophan tail units and a phenylacetamide head as a trigger (Fig. 5.26) to evaluate disassembly in aqueous conditions. The phenylacetamide is selectively cleaved by the bacterial enzyme penicillin G amidase (PGA). The trigger was designed to disassemble through azaquinone methide rearrangement and cyclic dimethylurea elimination to release a phenol intermediate that will undergo six quinone methide elimination reactions to release the tryptophan tail units. 

With the advance of pharmaceutical science, it has been recognized that constant release is not the only way to maximize drug effectiveness and minimize side effects and that the assumptions used for constant release rate sometimes fail due to physiological conditions. From this perspective, zero-order dmg release is not acceptable in all cases and externally modulated or self-regulating dmg delivery systems have been developed as novel approaches to deliver dmgs as required. To realize such dmg delivery systems, it is important to constmct a system where the dmg itself senses environmental stimuli and responds appropriately to control the dmg release. For this purpose, the phase transition polymers have been intensively exploited as a candidate material during last decade [21]. 

In a strict self-assembly process, the final product is produced entirely spontaneously when the components are mixed together in the correct ratios under a given set of conditions of temperature, pH, concentration etc. The product formation must be completely reversible and represent the thermodynamic minimum for the system. In essence, all the information necessary for the assembly to occur is coded into the constituent parts. The concept of strict self-assembly is rooted in the Thermodynamic Hypothesis of Afinison who suggested that under physiological conditions the native structure of a protein is... 

Stupp, S.I., Hartgerink, J.D., and Beniash, E. Self-Assembly of Peptide-Amphiphile Nanofibers Under Physiological Conditions for Biomedical Applications, 2003-US4779 2003070749 (2003b). 

The emission of Trp 19 in melittin shifts to the red side peaking at 341 nm (Fig. 18), and the probe location slightly moves away from the lipid interface toward the channel center. Consistently, we observed a larger fraction of the ultrafast solvation component (35%) and a smaller contribution of slow ordered-water motion (38%). Melittin consists of 26 amino acid residues (Fig. 9), and the first 20 residues are predominantly hydrophobic, whereas the other 6 near the carboxyl terminus are hydrophilic under physiological conditions. This amphipathic property makes melittin easily bound to membranes, and extensive studies from both experiments [156-161] and MD simulations [162-166] have shown the formation of an 7-helix at the lipid interface. Self-assembly of 7-helical melittin monomers is believed to be important in its lytic activity of membranes [167-169]. Our observed hydration dynamics are consistent with previous studies, which support the view that melittin forms an 7-helix and inserts into the lipid bilayers and leaves the hydrophilic C-terminus protruding into the water channel. The orientational relaxation shows a completely restricted motion of Trp 19, and the anisotropy is constant in 1.5 ns (Fig. 20b), which is consistent with Trp 19 located close to the interface around the headgroups and rigid well-ordered water molecules. 

The self-assembly process takes place under physiological conditions without the need of temperature changes [102, 103]. 

Interestingly, polysialic acid is a rather labile substance, which easily degrades spontaneously even under physiological conditions, due to an anomalously high p/f value of the internal sialic acid residues [258], This intramolecular self-cleavage may influence neuronal adhesion, embryogenesis and bacterial virulenee. 

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