Amino Acid Polymer Synthesis

This book is based predominantly on the patent literature and provides how to data regarding the production, purification, and application of commercial enzymes. Coverage is not limited to food applications, and 70 subjects are grouped as Enzymes, Enzymatic Processing, Enzyme Stabilization, Polymer-Enzyme Products, Cell Culture, Protein Analysis, Nucleic Acids etc.. Amino Acids, Peptide Synthesis, and Applications. Indexing includes U.S. patent number, company and patent assignee, inventor, and subject. 

Proteins are extraordinarily versatile molecules. They are found within cells and in extracellular locations. They may serve structural roles, as in collagen, or they may be functional as in enzymes, transporters, muscles, hormones, and receptors. Proteins are synthesized as linear polymers of 19 amino acids and one imino acid (commonly referred to slightly inaccurately as 20 amino acids). After synthesis of the initial polymer, or polypeptide, the protein may be ready for its function, or additional chemical modification of the structure may occur. In virtually all cases, specific folding of the protein into a fixed three-dimensional structure is also required. Proteins, together with RNA and polysaccharides, play a major role in their own synthesis, modification, and folding. 

Today, the evolution of genes, programmed cell death (apoptosis), and the action of messenger RNA (mRNA) are three major targets of research. mRNA contains the blueprint for every protein in the body. It is transcribed from a DNA template, and carries information to ribosomes, the sites of protein synthesis. The sequences of nucleic acid polymers are translated by transfer RNA (tRNA) into amino acid polymers. tRNA recognizes the three-nucleotide sequences that encode each amino acid. Ribosomal RNA directs the ribosome s production of proteins. Codons carry the messages that terminate protein synthesis. 

Lowe, C. U., Rees, M. W. and Markham, R. (1963) Synthesis of complex organic compounds from simple precursors formation of amino acids, amino acid polymers, fatty acids and purines from ammonium cyanide. Nature, 199, 219-222. 

Used in the synthesis ot bioactive peptides in water-organic solvent mixtures and ionic liquids substrate-mimetic-mediated coupling ot long fragments [3-7] amino acid polymers tor biomaterials [8]... 

Then N-Boc-O-benzylserine is coupled to the free amino group with DCC. This concludes one cycle (N° -deprotection, neutralization, coupling) in solid-phase synthesis. All three steps can be driven to very high total yields (< 99.5%) since excesses of Boc-amino acids and DCC (about fourfold) in CHjClj can be used and since side-reactions which lead to soluble products do not lower the yield of condensation product. One side-reaction in DCC-promoted condensations leads to N-acylated ureas. These products will remain in solution and not reaa with the polymer-bound amine. At the end of the reaction time, the polymer is filtered off and washed. The times consumed for 99% completion of condensation vary from 5 min for small amino acids to several hours for a bulky amino acid, e.g. Boc-Ile, with other bulky amino acids on a resin. A new cycle can begin without any workup problems (R.B. Merrifield, 1969 B.W. Erickson, 1976 M. Bodanszky, 1976). 

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... 

FIGURE 1.9 (a) Amino acids build proteins by connecting the n-carboxyl C atom of one amino acid to the n-amino N atom of the next amino acid in line, (b) Polysaccharides are built by combining the C-1 of one sugar to the C-4 O of the next sugar in the polymer, (c) Nucleic acids are polymers of nucleotides linked by bonds between the 3 -OH of the ribose ring of one nucleotide to the 5 -P04 of its neighboring nucleotide. All three of these polymerization processes involve bond formations accompanied by the elimination of water (dehydration synthesis reactions). 

Polymer-supported esters are widely used in solid-phase peptide synthesis, and extensive information on this specialized protection is reported annually. Some activated esters that have been used as macrolide precursors and some that have been used in peptide synthesis are also described in this chapter the many activated esters that are used in peptide synthesis are discussed elsewhere. A useful list, with references, of many protected amino acids (e.g., -NH2, COOH, and side-chain-protected compounds) has been compiled/ Some general methods for the preparation of esters are provided at the beginning of this chapter conditions that are unique to a protective group are described with that group/ Some esters that have been used as protective groups are included in Reactivity Chart 6. 

It is also possible to prepare them from amino acids by the self-condensation reaction (3.12). The PAs (AABB) can be prepared from diamines and diacids by hydrolytic polymerization [see (3.12)]. The polyamides can also be prepared from other starting materials, such as esters, acid chlorides, isocyanates, silylated amines, and nitrils. The reactive acid chlorides are employed in the synthesis of wholly aromatic polyamides, such as poly(p-phenyleneterephthalamide) in (3.4). The molecular weight distribution (Mw/Mn) of these polymers follows the classical theory of molecular weight distribution and is nearly always in the region of 2. In some cases, such as PA-6,6, chain branching can take place and then the Mw/Mn ratio is higher. 

Our interest in the synthesis of poly (amino acids) with modified backbones is based on the hypothesis that the replacement of conventional peptide bonds by nonamide linkages within the poIy(amino acid) backbone can significantly alter the physical, chemical, and biological properties of the resulting polymer. Preliminary results (see below) point to the possibility that the backbone modification of poly(amino acids) circumvents many of the limitations of conventional poly(amino acids) as biomaterials. It seems that backbone-modified poly (amino acids) tend to retain the nontoxicity and good biocompatibility often associated with conventional poly (amino acids)... 

The easy processibility of hydroxyproline-derived polyesters is in marked contrast to the unfavorable material properties of most conventional poly (amino acids) that cannot usually be processed into shaped objects by conventional polymer-processing techniques (7). Furthermore, since the synthesis of poly(N-acylhydroxyproline esters) does not require the expensive N-carboxyanhydrides as monomeric starting materials, poly(N-acylhydroxyproline esters) should be significantly less expensive than derivatives of conventional poly(hy-droxyproline). 

Lu H, Wang J, Lin Y, Oieng J (2009) One-pot synthesis of brush-like polymers via integrated ring-opening metathesis polymerization and polymerization of amino acid N-carboxyanhy-drides. J Am Oiem Soc 131 13582-13583... 

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