Peptides equilibrium with amino acids

The availability of copper in the body is somewhat different from that of iron. Copper in the Mood serum is bound in caeruloplasmin, Excessive dietary copper is predominately carried by serum albumin. Serum albumin copper is in the equilibrium with low molecular mass complexes of amino acids or small peptides. Unfortunately, the concentration of such complexes is below the detection limit. Regardless of the... 

Depicted in Fig. 2, microemulsion-based liquid liquid extraction (LLE) of biomolecules consists of the contacting of a biomolecule-containing aqueous solution with a surfactant-containing lipophilic phase. Upon contact, some of the water and biomolecules will transfer to the organic phase, depending on the phase equilibrium position, resulting in a biphasic Winsor II system (w/o-ME phase in equilibrium with an excess aqueous phase). Besides serving as a means to solubilize biomolecules in w/o-MEs, LLE has been frequently used to isolate and separate amino acids, peptides and proteins [4, and references therein]. In addition, LLE has recently been employed to isolate vitamins, antibiotics, and nucleotides [6,19,40,77-79]. Industrially relevant applications of LLE are listed in Table 2 [14,15,20,80-90]. 

FIGURE 7.31 Aminolysis of a succinimido ester by (A) an amino-acid anion generated by base [Anderson et al., 1974] and (B) a peptide anion that is in equilibrium with the peptide.114 Pg = protecting group. Appropriate solvents are tetrahydrofuran, acetone, or dimethylforma-mide with water. 

Saturated 5(4//)-oxazolones are easily obtained from //-acylamino acids in the presence of a cyclization agent and have been used extensively in coupling reactions as synthetic equivalents of a-amino acids in the synthesis of peptides. In this context, tautomeric equilibrium can be a significant problem due to the racemization associated with the isomerization. For example, trifluoroacetylation of tryptophan in ether affords the 5(4//)-oxazolone 5 without racemization. However, upon dissolution in acetonitrile, 5 completely racemizes. Further, upon heating, an aqueous dioxane solution of 5 cleanly isomerizes to the isomeric 5(2//)-oxazolone 6 (Scheme 7.2). 

Here Vij denotes the distance between atoms i and j and g(i) the type of the amino acid i. The Leonard-Jones parameters Vij,Rij for potential depths and equilibrium distance) depend on the type of the atom pair and were adjusted to satisfy constraints derived from as a set of 138 proteins of the PDB database [18, 17, 19]. The non-trivial electrostatic interactions in proteins are represented via group-specific dielectric constants ig(i),g(j) depending on the amino-acid to which atom i belongs). The partial charges qi and the dielectric constants were derived in a potential-of-mean-force approach [20]. Interactions with the solvent were first fit in a minimal solvent accessible surface model [21] parameterized by free energies per unit area (7j to reproduce the enthalpies of solvation of the Gly-X-Gly family of peptides [22]. Ai corresponds to the area of atom i that is in contact with a ficticious solvent. Hydrogen bonds are described via dipole-dipole interactions included in the electrostatic terms... 

Refolding is generally found to proceed by a series of exponential phases. Many of these exponentials are a consequence of cis-trans isomerization about peptidyl-prolyl bonds.14,15 The equilibrium constant for the normal peptide bond in proteins favors the trans conformation by a factor of 103-104 or so. The peptidyl-prolyl bond is an exception that has some 2-20% of cis isomer in model peptides (see Chapter 1, Figure 1.3). Further, it is often found as the cis isomer in native structures. (Replacement of ds-prolines with other amino acids by protein engineering can retain the cis stereochemistry.16) The interconversion of cis to trans in solution is quite slow, having half-lives of 10-100 s at room temperature and neutral pH. This has two important consequences. First, a protein that has several... 

Salt induced peptide formation [108] is based on a dehydrating activity of concentrated NaCl solutions in which free water molecules are less available, which drives the equilibrium towards peptide formation. This change in the thermodynamic barrier is coupled to a decrease of the kinetic barrier owing to the addition of a Cu(II) salt catalyst. A complex of copper with two amino acid ligands 14 has been proposed to be responsible for the catalytic process. In this way, the reaction between two amino acid ligands leading to peptide bond formation can take place intramolecularly ... 

We can also get some information by comparing the modern biosynthetic pathways to the capabilities of prebiotic chemistry. Amino acids are usually activated in living organisms by reaction with ATP both through the ribosomal and non-ribosomal peptide synthesis pathways. Amino acyl fRNA synthetases bind ATP and free amino acids to cause the highly unfavorable adenylate anhydride formation to be close to equilibrium in the active site. 

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