Amino acid-attached polymers

The amino acid attached to a polymer is treated with an vV-protected, carboxyl-activated amino acid to give the supported peptide. In the following reaction the triazolide was formed in situ from the p-nitrophenyl ester and 1,2,4-triazole 1341... 

The addition of phenylalanine to the previously described starch base materials (Control and Oxidized starches) was done on a lOX (w/w) level for covalent attachment. The Oxidized starch was apparently more conductive to cyanogen bromide activation for amino acid attachment than was the Control starch (92X attachment versus 67X, respectively). The addition of aspartame was also completed for the Oxidized (ii) starch polymer on a level of... 

Another advantage of the solid phase method is that the steps are repetitive and can be automated. An automatic peptide synthesizer is commercially available. It consists of a flask with a fritted-glass filter at the bottom along with bottles containing solutions of BOC-protected amino acids and the other necessary reagents and wash solutions. The polymer with the first amino acid attached is placed in the flask, and the order of... 

Unlike reagents bound to crosslinked polymeric supports, soluble macromolecules are able to interact with reactive groups attached to insoluble polymers. This fact was demonstrated by Frank and Hagenmaier, who developed an alternating liquid-solid phase peptide synthesis procedure. Amino acids attached to crosslinked polystyrene via a carbamate linker were condensed with a peptide ester of polyethyleneglycol monostearylether (Scheme 1.6.12). 

Table 16.5 Hydrolysis of methyl esters of a-amino acids attached to macronet isoporous polymer (CMDP, 5% - Support I) and styrene-0.8% DVB copolymer (Support II) [379]...

A special case of deletion is the simultaneous loss of two residues, the amino acid attached via an ester bond to the polymer together with the penultimate residue. The known tendency of dipeptide esters for cyclization is responsible for this side reaction. Elimination of the two residues as a diketopiperazine... 

The design and application of new polymer supports for peptide synthesis remains a rapidly developing field. The use of glass beads coated with the polystyrene chloromethylated resin in a packed bed has been studied in detail. With a model tetrap>eptide the procedure was developed to a point where it became ten times faster than the usual Merrifield method but the average yield of each amino acid attachment was about 98.8% and the tetrapeptide... 

The steps in a Merrifield synthesis are summarized for a dipeptide in Figure 17.7. In step 1, the polymer is first treated with an N-protected amino acid. The carboxylate ion acts as an oxygen nucleophile and displaces the chloride ion from the polymer, thus forming an ester link. The first amino acid attached to the polymer will eventually become the C-terminal amino acid of the synthetic peptide. 

The actual process of solid-phase peptide synthesis, outlined in Figure 27.15, begins with the attachment of the C-terminal amino acid to the chloromethylated polymer in step 1. Nucleophilic substitution by the carboxylate anion of an A-Boc-protected C-terminal... 

Amino acids, the building blocks of giant protein molecules have a carboxyl group and an amino group attached to the same carbon atom. A protein is a linear polymer of amino acids combined by pepfide linkages. Twenfy different amino acids are common in proteins. Their side chains, which have a variety of chemical properties, control the shapes and functions of proteins. Some of these side chains are hydrophobic, others are hydrophilic, and still others occur either on the surface or the interiors of proteins. 

Phosphazene polymers can act as biomaterials in several different ways [401, 402,407]. What is important in the consideration of skeletal properties is that the -P=N- backbone can be considered as an extremely stable substrate when fluorinated alcohols [399,457] or phenoxy [172] substituents are used in the substitution process of the chlorine atoms of (NPCl2)n> but it becomes highly hydrolytically unstable when simple amino acid [464] or imidazole [405-407] derivatives are attached to the phosphorus. In this case, an extraordinary demolition reaction of the polymer chain takes place under mild hydrolytic conditions transforming skeletal nitrogen and phosphorus into ammonium salts and phosphates, respectively [405-407,464]. This opens wide perspectives in biomedical sciences for the utilization of these materials, for instance, as drug delivery systems [213,401,405,406,464] and bioerodible substrates [403,404]. 

The structural versatility of pseudopoly (amino acids) can be increased further by considering dipeptides as monomeric starting materials as well. In this case polymerizations can be designed that involve one of the amino acid side chains and the C terminus, one of the amino acid side chains and the N terminus, or both of the amino acid side chains as reactive groups. The use of dipeptides as monomers in the manner described above results in the formation of copolymers in which amide bonds and nonamide linkages strictly alternate (Fig. 3). It is noteworthy that these polymers have both an amino function and a carboxylic acid function as pendant chains. This feature should facilitate the attachment of drug molecules or crosslinkers,... 

Covalent chemical attachment of an enzyme to an electrode or a polymer coating requires mild and specific chemistry to react with amino acids in the protein in aqueous... 

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