Polymeric supports insoluble

Peptide synthesis requires the use of selective protecting groups. An N-protected amino acid with a free carboxyl group is coupled to an O-protected amino acid with a free amino group in the presence of dicydohexvlcarbodi-imide (DCC). Amide formation occurs, the protecting groups are removed, and the sequence is repeated. Amines are usually protected as their teit-butoxy-carbonyl (Boc) derivatives, and acids are protected as esters. This synthetic sequence is often carried out by the Merrifield solid-phase method, in which the peptide is esterified to an insoluble polymeric support. 

A stoichiometric forerunner of this approach was the wolf and lamb reaction, reported by Patchornik and co-workers in 1981 [17]. Two reagents that in solution react with each other quickly to give an undesired product (hence wolf and lamb ) were immobilized on solid polymeric supports (two insoluble and mutually immiscible polymers, Scheme 5.1), rendering them unreactive towards each other. This allowed the formation of the desired product through the use of a messenger reagent. 

It has long been recognized that polymeric supports for oligosaccharide synthesis do not need to be insoluble.33 Wang et al. applied the sulfoxide glycosylation method to the synthesis of disaccharide 79 (Scheme 3.14). The key feature of this work was the base-labile linker. Sulfoxide 74 was used to glycosylate polyethylene glycol... 

Oligosaccharide syntheses employing enzymatic reactions would in principle greatly benefit from being performed on a polymer support since the support might effectively facilitate isolation of the final product. Presumably, a water-soluble polymeric support will be preferable to any insoluble support since reaction rates could otherwise become too slow. Glycosidases as synthetic enzymes would be the best candidates to study this type of the enzymic approach to oligosaccharide synthesis. 

In general, both soluble and insoluble (solid) polymeric supports can be used for this purpose, however, nowadays insoluble polymeric supports are more frequently being used because they are easy to automate. 

Traditionally, soluble polymers have received less attention as polymeric supports than their insoluble counterparts. A perceived problem with the use of soluble polymers rested in the ability to isolate the polymer from all other reaction components. Yet, in practice this separation is not difficult and several methods have capitalized on the macromolecular properties of the soluble support to achieve product separation in liquid-phase synthesis. Most frequently the homogeneous... 

A frequent complication in the use of an insoluble polymeric support lies in the on-bead characterization of intermediates. Although techniques such as MAS NMR, gel-phase NMR, and single bead IR have had a tremendous effect on the rapid characterization of solid-phase intermediates [27-30], the inherent heterogeneity of solid-phase systems precludes the use of many traditional analytical methods. Liquid-phase synthesis does not suffer from this drawback and permits product characterization on soluble polymer supports by routine analytical methods including UV/visible, IR, and NMR spectroscopies as well as high resolution mass spectrometry. Even traditional synthetic methods such as TLC may be used to monitor reactions without requiring preliminary cleavage from the polymer support [10, 18, 19]. Moreover, aliquots taken for characterization may be returned to the reaction flask upon recovery from these nondestructive... 

Many different soluble polymers have been used as supports for catalyst immobilization. Since solvation of otherwise insoluble catalysts can frequently be accom-pHshed by attachment to a soluble polymer, these supports have found significant use in the immobihzation of classical solution phase catalysts. Here, we will only survey polyethylene glycol (PEG) as a soluble polymeric support for catalysis. The use of other types of soluble polymers (e.g., polyethylene, non-cross-linked polystyrene) has been reviewed elsewhere [49]. 

Polypyrrol is a polymeric support that can be used in immobilization of ONDs to surfaces. The generation of polypyrrol films can be by electrochemical co-polymerization of pyrrole and pyrrole-modified ONDs onto platinum electrodes. The polymer forms a black and insoluble film that is electrically conducting and whose thickness depends on the current used during the polymerization process (Fig. 14). The final surface density of the OND can be controlled by the ratio of pyrrole/OND being polymerized [53-55]. 

The most commonly used strategies for preparing ureas on insoluble supports are outlined in Figure 14.2. The reaction conditions are similar to those used in solution as most of the reagents required are compatible with the widely used polymeric supports. 

Four methods have been developed for enzyme immobilization (1) physical adsorption onto an inert, insoluble, solid support such as a polymer (2) chemical covalent attachment to an insoluble polymeric support (3) encapsulation within a membranous microsphere such as a liposome and (4) entrapment within a gel matrix. The choice of immobilization method is dependent on several factors, including the enzyme used, the process to be carried out, and the reaction conditions. In this experiment, an enzyme, horseradish peroxidase (donor H202 oxidoreductase EC 1.11.1.7), will be imprisoned within a polyacrylamide gel matrix. This method of entrapment has been chosen because it is rapid, inexpensive, and allows kinetic characterization of the immobilized enzyme. Immobilized peroxidase catalyzes a reaction that has commercial potential and interest, the reductive cleavage of hydrogen peroxide, H202, by an electron donor, AH2 ... 

General scheme for synthesis on an insoluble polymeric support... 

For further elongation of the peptide chain, successive coupling reactions with other polymeric active esters may be carried out until the desired sequence is obtained. The polymeric active esters are prepared by the attachment of the N-protected amino acids or peptides to a suitable insoluble polymer. Potentially useful polymeric supports in this case should carry a free hydroxyl function to which the carboxyl group of the amino acid derivatives may be coupled. Crosslinked poly(4-hydroxy-3-... 

The major drawbacks of the synthesis of peptides on insoluble polymeric supports, when the traditional linear approach is applied, derive from the difficulty of purifying the various synthetic intermediates. First of all, this limitation has an impact on the synthesis of very large compounds.It is easy to calculate that the maximum overall yield that can be achieved in the synthesis of a 20-residue peptide, if the mean yield per cycle is 90%, is only 12% (0.90 ° X 100). A mean yield per cycle of 99% affords a modest overall 37% yield in the synthesis of a peptide of 100 amino acids (see Table 1). 

The use of insoluble polymeric carriers has greatly simplified the synthesis of peptides purification of the growing peptide chain in the repetitive steps is achieved by filtration procedures that simply remove all soluble reagents and byproducts from the reaction medium, whilst the covalently resin-hnked macromolecule is retained on the insoluble polymeric support. In all sohd-phase reactions of this type, the polymeric support represents the medium on or in which the chemical reaction takes place. Correspondingly, this medium is represented by the total amount of insoluble polymer present, which in the case of polymeric beads is divided into small, individual reaction compartments. Resin parameters such as the degree of crosshnking, the polarity of the resin, its sweUing properties, mass-transport, phase transitions, bead size, and the particle size distribution therefore have to be taken into serious consideration. 

Polymers have been used since the last two decades for the immobilization of enzymes, and a number of articles have been publi ed on the plication of insoluble polymeric supports for the immobflization of enzymes ggsj gg applica-... 

Most of the earlier studies on the immobilization of enzymes were directed towards the attachment of the enzymes to water-insoluble polymeric supports such as cellulose dextran derivatives, polyacrylamide and porous glass Diffusion problems and steric hindrance are two main factors affecting the application of such supports. The introduction of soluble polymers for immobilization purposes overcomes these difficulties to a greater extent. These soluble enzyme derivatives were synthesized in order to increase the effective molecular size of parent en mes this would rmit the use of ultrafiltration without any los of the enzyme. O NeiD etal. immobilized the enzyme chymotrypsin on soluble dextran for... 

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