Amino acyl adenylates

Microparticles composed of each of four homopolyribonucleotides and the same lysine-rich proteinoid is found to influence the incorporation of individual amino-acyl adenylate 59). The incorporation favors the amino acids whose codons are related to the nucleotide in the particles (Fig. 6), when conditions are appropriately chosen. Other conditions yield other preferences. These results support a stereochemical basis for the genetic code. 

Among activated forms of amino acids, mixed anhydrides with inorganic phosphate or phosphate esters require a special discussion because they are universally involved in peptide biosynthesis through the ribosomal and non-ribosomal pathways. These mixed anhydrides have stimulated studies in prebiotic chemistry very early in the history of this field. Amino acyl adenylates 18c have been shown to polymerize in solution [159,160] and in the presence of clays [139]. However, their participation as major activated amino acid species to the prebiotic formation of peptides from amino acids is unlikely for at least two reasons. Firstly, amino acid adenylates that have a significant lifetime in aqueous solution become very unstable as soon as either CO2 or bicarbonate is present at millimolar concentration [137]. Lacey and coworkers [161] were therefore conduced to consider that CO2 was absent in the primitive atmosphere for aminoacyl adenylate to have a sufficient lifetime and then to allow for the emergence of the modern process of amino acid activation and of the translation apparatus. But this proposition is unlikely, as shown by the analysis of geological records in favor of CO2 contents in the atmosphere higher than present levels [128]. It is also in contradiction with most studies of the evolution of the atmosphere of telluric planets [30,32], Secondly, there is no prebiotic pathway available for adenylate formation and ATP proved to be inefficient in this reaction [162]. 

Amino acyl adenylates are obtained in the reaction of adenosine 5-phosphate (ASP) with free amino acids in aqueous pyridine, mediated by DCC. The linkage is an anhydride between the amino acid carboxyl group and the phosphate in A5P." ... 

An enzyme has been isolated from the FK520 producer which is believed to be the key one responsible for inserting pipecolic acid into the macrocycle [114]. It is reported to be dimeric and activates pipecohc acid and several structural analogues in an ATP-dependent reaction to give an enzyme-bound amino-acyl adenylate. There is evidence that this then reacts to form a thioester linkage to the enzyme. This mechanism of activation is the same as that found in the non-ribosomal biosynthesis of peptide natural products such as gramicidin [112]. 

The biosynthesis of a variety of biologically active peptides proceeds nucleic acid-free on protein templates (IK Peptide synthetases generally activate an acceptor amino acid by formation of amino-acyl adenylates or phosphates, which will be stabilized in an enzyne-aminoacylation step, similar as in tRNA-aminoacylation. Reaction with a donor peptide, which may be covalently bound, leads to a specific chain elongation. While small peptides like glutathione are formed by "one-step"-synthetases, more complex structures like gramicidin S are produced by multienzvme systems, which may contain multifunctional polypeptides. Characteristic features of such systems are 1.)activation as aminoacyl adenylates, 2.) aminoacylation of enzyme thiol-groups, 3.) covalently bound peptide intermediates and 4.) a specific intrinsic transport mechanism similar to the biosynthesis of fatty acids. 

J. Vater, and H. Kleinkauf, Substrate specificity of the amino-acyl adenylate activation sites of gramicidin S-synthetases,... 

The second step in protein synthesis is the binding of the amino acid to RNA. If one places free amino acyl adenylate (labeled in the amino acid) in the presence of the RNA prepared from the supernatant fluid, the RNA will be labeled. The labeling is low because the acyl adenylate degrades rapidly in the absence of its enzyme. The enzymes responsible for transferring... 

At least three stages are now believed to be involved in protein synthesis in animal cells. In stage (j), amino acids (AA) are activated by the formation of amino acyl adenylates in the presence of appropriate activating enzymes (E). In stage (2), the activated amino acid reacts with ribonucleic acids of relatively low molecular weight, known as soluble (or transfer) ribonucleic acids (sRNA). In stage (j), the amino acid is transferred to the RNA of the microsomes (Ms) where it is incorporated into new protein ... 

Characteristic feature of the peptide synthetase systems is that the activation reaction of each amino acid substrate, i.e. amino acyl adenylate and thioester... 

Berg, P. (1958) The chemical synthesis of amino acyl adenylates. J. Biol. Chem. 233, 608. 

Alternative routes for the prebiotic synthesis of oligo- and polypeptides in aqueous systems, at relatively low temperatures, may well have involved activated monomers like oc-amino nitriles, a-amino amides or amino acyl adenylates. Interesting results were obtained earlier with the first two types of compounds in our laboratory and other laboratories. More recently the amino acyl adenylates, in the presence of montmorillonite and at pH... 

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