Phosphoester

ATP is hydrolyzed in at least two consecutive steps on F-actin, viz. cleavage of the y-phosphoester bond, followed by Pj release, according to the following scheme ... 

Wang S, Andrew CA, et al. A new nerve guide conduit material composed of a biodegradable poly (phosphoester). Biomaterials, 2001, 22, 1157-1169. 

While hydrolysis is a thermodynamically favored reaction, the amide and phosphoester bonds of polypeptides and ohgonucleotides are stable in the aqueous environment of the cell. This seemingly paradoxic behavior reflects the fact that the thermodynamics governing the equihbrium of a reaction do not determine the rate at which it will take place. In the cell, protein catalysts called enzymes are used to accelerate the rate... 

Synthesis and Characterization of Hydrolytically Labile Poly(phosphoester—urethanes)... 

Biodegradable poly(phosphoester-urethanes) containing bisglycophosphite as the chain extender were synthesized. Methylene bis-4-phenyl isocyanate (MDI) and toluene diisocyanate (TDI) were initially used as diisocyanates. Since there was a concern that the degradation products could be toxic, the ethyl 2,6-diisocyanatohexanoate (LDI) was synthesized and replaced the MDI (or TDI). The hydrolytic stability and solubility of these polymers were tested. Preliminary release studies of 5-fluorouracil from MDI based poly(phosphoester-urethane) and methotrexate from LDI based poly(phosphoester-urethane) are also reported. 

Our interest in the past few years has been on biodegradable polymers. We have been evaluating the potential of poly(phosphoesters) as degradable biomaterials (4).We were attracted to this class of polymers because the phosphoester bond in the backbone is cleavable under physiological conditions, the presence of the P-O-C group would facilitate fabrication, and the versatile chemical structure affords a wide... 

Table I. The chemical structures used in the synthesis of poly(phosphoester-urethanes)...

Figure 1 Molecular weight distribution of PLU-1 poly(phosphoester-urethane).

The in vitro degradation profiles of several TDI poly(phosphoester-ure thanes) are shown in Figure 2. It is not possible from this study to correlate the decomposition kinetics with the chemical structure, except for the fact that biodegradability is demonstrated. The in vitro release of 5-FU from PPU-7 is shown in Figure 3. After an initial burst, a reasonably steady and sustained release followed. The UV spectrum of the released 5-FU was identical to that of pure 5-FU, suggesting the chemical integrity of the drug. 

Figure 2 Hydrolytic degradation of poly(phosphoester-urethanes) based on TDI.

Figure 5 Weight loss of lysine based poly (phosphoester urethanes) at 7 days in 0.1M pH 7.4 phosphate "buffer at 37°C.

Biodegradable polyurethanes have been proposed and studied before (9-72). The difference in our study is the inclusion of a phosphoester linkage instead of the commonly used polyester component. This seems to provide more flexibility as the side chain of the phosphate or phosphonate can be varied. For controlled drug delivery applications, drugs can be linked to this site to form a pendant delivery system. Moreover, for certain medical applications, fast degradation rate is obtainable by the introduction of these hydrolyzable phosphoester bonds. With the LDI based polyurethanes, drugs or other compounds of interest can also be coupled to the ester side chain of the lysine portion. 

Urethane hydrolyzes into an amine, an alcohol, and carbon dioxide. So the possible degradation products of a poly(phosphoester-urethane) are diamines, diols, phosphates, carbon dioxide, and even ureas. Urea is possible because the isocyanate is extremely sensitive to moisture, which would convert the isocyanate to an amino group. One is therefore bound to have traces of diamine in the polymerization that leads to a urea bond in the backbone. We think the cytotoxicity seen in the macrophage functional assay comes from the TDI structure. 

Recently, highly branched macromolecular polyamidoamine dendrimers have been prepared with Co11 bound where the metal ions have additional exchangeable coordination sites.450 These macromolecules show a capacity for catalyzing the hydrolysis of phosphate esters, presumably via intermediate bound phosphoester species. 

Scheme 3.5, and carotenoids have been previously incorporated into vesicles of phospholipids, Figure 3.1 (Milon et al. 1986, Britton 1998). It was therefore reasonable to connect carotenoids with a phosphate group, above all because hydrophobic phosphate esters had previously been synthesized (Sliwka 1997). The C30-monoglyceride, 3.12, was therefore used as an educt for the synthesis of the zwitterionic, hydrophobic C30-lysophosphocholine, 3.15, via aminolyse of the bromo phosphoester,... 

Conversion of Amines to Phosphoesters n-Decyl Diethylphosphate. N. Nikolaides, I. Schipor, and B. Ganem, Department of Chemistry, Cornell University, Ithaca, NY 14853... 

Fig. 2. (A) Nerve guide conduit from the poly(phosphoester), poly(bis(hydroxyethyl) terepthalate-ethyl ortho-phosphate/terephthaloyl chloride) (Mw 14,900, solution concentration 34% (w/w), immersion bath water, drying method freeze-drying) (B) cross-section of conduit showing distinct coating layers (C) cross-section of conduit with finger-like cavities. [Reproduced with permission from Wan et al. (2001).]...

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