Amino acids polymerisation

In order to join two amino acids with a peptide bond, a water molecule has to be removed, and this suggests immediately that the reaction should not easily take place in water. The energy balance does confirm, in fact, that amino acid polymerisation is not favoured in water, and we cannot expect therefore that the primitive broth would spontaneously produce a stable population of proteins. How then did these molecules appear ... 

It is of interest to note that catecholamine oxidation products have been shown to inhibit an in vitro amino acid polymerisation system from rat brain [383] and to inhibit polypeptide synthesis in E. coli [384]. 

Currently, a-amino acids are prepared by several routes such as by the fermentation of glucose, by enzyme action on several substances and by the hydrolysis of proteins. Many methods for synthesising the polymers are known, of which the polymerisation of A -carboxyanhydrides is of particular interest, as it yield-products of high molecular weight (Figure 18.24). 

This interpretation of the experimental results is not accepted by Clifford Matthews, who has for many years defended the following hypothesis the prebiotic proteins (or peptides) are formed from HCN by polymerisation reactions and not from single a-amino acids (see Chap. 5). The necessary preconditions for polycondensation of amino acids—high temperatures, acidic conditions and the absence of water—were not present on primeval Earth. 

The stepwise polymerisation of activated amino acids leads to the formation of activated dimers, which very often cyclise to diketopiperazines and are thus removed from the chain elongation process (Orgel, 1989). 

The addition of ammonia to the variety of acids derivable from either the breakdown of glucose, glycolysis, or of the pentose shunt reaction products, ribose and NADPH, and from the citrate cycle, gives the amino acids (see Table 4.7 and Figure 4.4) Polymerisation of amino acids in cells gives proteins. In some of the amino acids sulfur and selenium can be incorporated easily. We assume NH3 was present. (Note that Se is in a coded amino acid not in Table 4.7.) Some selective metal-binding properties can be seen in Table 4.7, but amino acid carboxylates can bind all. 

Taking this one step further, perhaps even an inorganic gene may have been provided by clay mineral sources. Earliest clay samples are of a mineral called montmorillonite that consists of sheets of aluminosilicates in which Fe2+, Fe3+ and Mg2+ are substituted for some of the Al3+, and Al3+ is substituted for Si4+. The oxygen content of the layers does not change and the alternative valencies allow the production of positive and negatively charged layers. Dramatically, Paecht-Horowitz and co-workers showed that the amino acid adenylate could be polymerised with up to 50 units on the montmorillonite surface in aqueous solution. Similar condensation reactions for carbohydrates on hydrotalcite surfaces have... 

Endogenous organic synthesis Urey-Miller experiments as a source of prebiotic molecules via the Strecker synthesis for amino acids, HCN polymerisation for purines and pyrimidines and the formose reaction for sugars... 

Polyamino acids are easy to prepare by nucleophUe-initiated polymerisation of amino acid JV-carboxyanhydrides. Polymers such as poly-(L)-leucine act as robust catalysts for the epoxi-dation of a wide range of electron-poor alkenes, such as y-substituted a,Ji-unsaturated ketones. The optically active epoxides so formed may be transformed into heterocyclic compounds, polyhydroxylated materials and biologically active compounds such as dUtiazem and taxol side chain. 

Before polymerisation can take place, the free amino acid must be protected and activated. This is most commonly achieved by preparing the N-carboxyanhydri-de (NCA) as depicted in Scheme 4. 

Many enzymes in the cell are organised into sequences, so that the reactions they catalyse are integrated into pathways or processes. In these pathways, a precursor or substrate is converted to a product, e.g. glucose is converted to lactic acid amino acids are polymerised to form protein glutamine is converted to aspartate. These pathways have both a thermodynamic and a kinetic structure. The thermodynamic structure is presented in Chapter 2. The kinetic structure is described here. There are three basic facts that must be appreciated before the kinetic structure is explained. 

A protein known as the amyloid precursor protein (APP) spans the plasma membrane of the neurone. It possesses an extracellular domain but its function is unknown. The extracellular domain is partially hydrolised by proteolytic enzymes, known as secretases. One of the products is the amyloid peptide, of which there are two forms. The larger form, contains 42 amino acids and readily polymerises to form plaques in the extracellular space, damaging the neurones. Some sufferers possess a mutated form of the APP protein which more readily produces the larger peptide upon proteolysis, so that more toxic plaques are produced. It is the progressive accumulation of these plaques that is considered to be one cause of Alzheimer s disease. 

The relationship between the base sequence in DNA and the amino acid sequence in the protein is known as the genetic code. With four bases (A, C, G and T) 64 three-base combinations are possible to provide the code for the amino acids (e.g. GTA, CCG). All but three of these are used to code for the polymerisation of the 20 different amino acids (in fact, 21, see Chapter 8) to form a polypeptide chain that can then form a protein. Most amino acids are, therefore, coded for by more than one three-base combination (Appendix 20.2). The link between the three-base... 

Figure 20.20 Summary of transcription, RNA processing and polypeptide synthesis. Polymerisation of the DNA template by RNA polymerase produces pre-mRNA (the primary transcript) this is transcription. The pre-mRNA is now processed, which involves capping, polyadenylation, editing and splicing (see text). The resultant mRNA transfers from the nucleus to the cytosol, where amino acids are polymerised to produce a polypeptide using the instructions present in the codons of the mRNA.

These polymers possessing amide linkages are Important examples of synthetle fibres and are termed as nylons. The general method of preparation eonslsts of the condensation polymerisation of diamines with dlearboxylle aelds and also of amino acids and their laetarns. 

Paechthorowitz, M. and Eirich, F. R. (1988). The polymerisation of amino acid adenilates on sodium montmorillonite with preadsorbed polypeptides. Orig. Life Evol Biosph., 18, 359-87. 

The exact action is not fully elucidated. However, bulaquine inhibits protein synthesis in protozoa and indirectly inhibits polymerisation of amino acids by the plasmodia. Treatment prevents emergence of either primary or secondary liver stage para-sitaemia and the disease. 

Szwarc.M. The Kinetics and Mechanism of N-carboxy-a-amino-acid Anhydride (NCA) Polymerisation to Poly-amino Acids. Vol. 4, pp. 1—65. 

Polymerisation of N-carboxy-cs-amino acid anhydrides to polypeptides represents an important and interesting process which yields polymers not easily produced by other techniques. This reaction, which has attracted the attention of many investigators and has been extensively studied during the last 20 years, proceeds through a chain polyaddition, i. e. the growth is determined by the sequence of steps P + M - -> Pn+1 rather than P + Pm y Pn+m (see however p. 39). The overall reaction proceeds through initiation and propagation steps and often it includes some termination. 

N-carboxy-a-amino-acid anhydrides react in a variety of ways and, therefore, it is difficult to discuss their polymerisation in a conventional manner, i. e. by separately considering the initiation, propagation and termination steps. It is believed that the reader more easily may comprehend its nature if the material is presented in terms of the chemical behaviour of the monomer towards various reagents. This course, therefore, will be followed in the subsequent sections. 

The Kinetics and Mechanism of NCA Polymerisation to Poly-amino Acids... 

Reaction with water produces an amino-acid which eventually initiates (28) the apparently normal amino-propagated polymerisation of NCA. The initiation and the hydrolysis are substantially slower than the propagation, e. g. at least a 600-fold water excess is required to... 

The inefficiency of water and of amino-acids in initiating the NCA polymerisation is now easily comprehended. The reaction has to be initiated by a base, whereas the amino-acids exist mainly in their zwitter-ion form. Hence, the initiation must be slow since it involves the non-ionised amino acid present only at low concentration. As the peptide grows in length, the equilibrium between the zwitter-ion and its non-ionised form shifts in iavour of the latter, and thus the rate of growth increases. This phenomenon contributes towards the auto-catalytic behaviour of this polymerisation. 

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