Chemistry and Biology of Proteins - F. Haurowitz 1953

Protein Synthesis
Amino Acid Polymerization

The polymerization of Amino Acids and simple Peptides under laboratory conditions can be achieved through various Methods. The polymerization of $\alpha$-aminocaproic acid is attained by heating [1]. Another, more convenient method used to obtain polyamino acids consists in the decarboxylation of carbamic anhydrides using small amounts of Water [2–5]:

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The products of such polymerization are typical Polypeptides containing amino acids joined by peptide bonds. They possess a very high molecular weight, roughly of the same order of magnitude as true Proteins. The close resemblance of these polymers to natural proteins is indicated, for example, by the fact that polylysine (the polymerization product of Lysine) is cleaved by Trypsin [6]. Poly-$\alpha$-glutamic acid obtained via polymerization proved to be similar to the natural Polyglutamic acid that constitutes the capsule of Bacillus anthracis [7, 8].

Polymers can also be obtained from a mixture of amino acids by treating them with one of the methods mentioned above. Thus, for instance, polymers of alanylglycylglycine containing 20 amino acid residues are formed upon heating the methyl esters of this tripeptide; they are cyclic peptides devoid of free terminal amino and carboxyl groups [9]. Polymer mixtures are obtained in a similar manner from mixtures of carbamic anhydrides if the latter are exposed to moist air [4]. It is interesting to note that the polymer of l-Alanine is insoluble in water, whereas a polymer consisting of a mixture of l- and d-alanine is soluble in water [10]. The insolubility of homogeneous poly-l-alanine indicates that its peptide chains are packed so compactly that water cannot penetrate between them, whereas the association of peptide chains in poly-dl-alanine appears to be quite loose, allowing water molecules to wedge freely between the CO and NH groups of the peptide framework [10].

Although none of the synthetic polypeptides has been found among natural compounds, the possibility of their formation in vitro is nevertheless of great biological interest. The ease of formation of these polymers indicates that the energy required for Peptide Synthesis cannot be very large; indeed, it amounts to only about 3,000 cal per mole of peptide bond [11].

The main differences between the polymerization reaction and in vivo Protein Synthesis are as follows: 1) in vivo protein synthesis takes place in an aqueous medium, whereas all polymerization reactions proceed exclusively in a medium containing only traces of water; 2) The formation of natural proteins involves molecules of 15–20 different amino acids, whereas the polymers are built from molecules of only one or a few amino acids. Moreover, if a mixture of many amino acids undergoes polymerization, it is impossible to determine the arrangement of amino acid residues within the peptide chain, and they are distributed randomly throughout the polypeptide molecule. In contrast, amino acids in natural proteins are arranged in a strictly defined order specific to each individual natural protein.