Dipeptides Gly-Ala

When applied to coupling two different amino acids, difficulty is to be expected because these same reactions can link two amino acids in a total of four different ways. Thus if we started with a mixture of glycine and alanine, we could generate four dipeptides, Gly-Ala, Ala-Gly, Gly-Gly, and Ala-Ala. 

Synthesis of polypeptides in the laboratory is much more complicated than the synthesis of the polyamides described in Chapter 24 because more than one monomer must be used and the order of their attachment must be carefully controHed. For example, suppose we want to prepare the dipeptide Gly-Ala. We cannot just heat a mixture of glycine and alanine. Although this would produce some of the desired dipeptide, it would also form a host of other products, including other dipeptides and tripeptides, as shown in the following equation ... 

Because amino acids have two functional groups, a problem arises when one attempts to make a particular peptide bond. For example, suppose you wanted to make the dipeptide Gly-Ala. That dipeptide is only one of four possible dipeptides that could be formed from alanine and glycine. 

The linking of two or more amino acids forms a peptide. A peptide bond is an amide bond that forms when the —COO group of one amino acid reacts with the H3N— group of the next amino acid. For example, the combination of the amino acids glycine and alanine produces an amide bond in the dipeptide Gly-Ala. The order of amino acids in the peptide is written as the sequence of three-letter abbreviations going from left to right. 

A peptide bond links glycine and alanine to form the dipeptide Gly-Ala. 

Reaction of HAuCU with the dipeptide glycylalanine (H-Gly-Ala-OH) and the tripeptide glycylalanylalanine (H-Gly-Ala-Ala-OH) gives the corresponding complexes [Au(Gly-Ala-0)Cl] (66) and [Au(Gly-Ala-Ala-O)] (67) where the peptides are coordinated to gold through — NH2, amide(s) and G02 groups in a near square... 

Amino acids used include Gly, Ala, Phe, Leu, His, co-aminoheptanoic acid, and Ala-His dipeptide. It was found that not only single amino acids were added to the dextran, but also poly(amino acid) chains formed during the reaction. 

As a simple example of a QM/MM Car-Parinello study, we present here results from a mixed simulation of the zwitterionic form of Gly-Ala dipeptide in aqueous solution [12]. In this case, the dipeptide itself was described at the DFT (BLYP [88, 89 a]) level in a classical solvent of SPC water molecules [89b]. The quantum solute was placed in a periodically repeated simple cubic box of edge 21 au and the one-particle wavefunctions were expanded in plane waves up to a kinetic energy cutoff of 70 Ry. After initial equilibration, a simulation at 300 K was performed for 10 ps. 

Tab. 1.3 Comparison between different sets of atomic point charges for a zwitterionic Gly-Ala dipeptide in aqueous solution. D-RESP electrostatic potential derived charges [12] fitted to all 36 configurations. Hirshfeld average value of the Hirshfeld charges [89c] along the full trajectory, Amber AMBER 1995 force field [86], Gromos GROMOS96 force field [85], The charges of equivalent atoms are imposed to be equal.

The QM dipole moment of the Gly-Ala dipeptide is, furthermore, reproduced by the D-RESP set within 2%. The predictivity of any D-RESP set on the dipole along the full trajectory is approximately 4%. This compares with predictivities of 6% and 7% for the dipoles computed with the AMBER 1995 and GRO-MOS96 force field charges, respectively. 

In a follow-up study, the effect of introduction of achiral Gly residues into the Ala-peptide chain (di- and tripeptides) on the afforded enantiomer separations was thoroughly investigated [123]. One of the major findings was that the introduction of a Gly residue compromised the enantioselectivity in particular if the Gly residue was located at the /V-terminus. For example, a-values (for all-5/all-7 enantiomers) decreased in the order Ala-Ala > Ala-Gly > Gly-Ala for the DNB-protected dipeptide... 

This reaction is known to be catalyzed by the enzyme oxynitrilase to produce the optically pure cyanohydrin 76). Since this reaction proceeds with a base catalyst, Jnoue et al. 75) used cyclic and linear dipeptides containing (S)-histidine. The catalysts employed are as follows benzyloxycarbonyl-R-(S)-histidine methyl ester with R = (S)-alanyl, (R)-alanyl, (S)-phenylalanyl,[Z-(S)-Ala-(S)-His-OCH3, Z-(R)-Ala-(S)-His-OCH3, and Z-(S)-Phe-(S)-His-OCH3] as linear dipeptides, and cyclic (S)-histidine containing dipeptides Gly—(S)—His,... 

Prepare a table of HPLC elution time values for each of the standard FMOC amino acids used in this experiment. FMOC amino acids usually elute from a reversed phase column in the following order (from first to last) Gly, Ala, Val, Phe, and Leu. Describe how the order of elution is related to the relative polarity of the FMOC amino acids. The FMOC reagent during the derivatization reaction often undergoes hydrolysis to a decar-boxylated form of FMOC. This product, an alcohol called FMOH, usually elutes from the HPLC column between Val and Phe or between Ala and Val. Use the standard elution times to identify the unknown amino acids present in the original dipeptide. 

Gly-Ala free of other possible dipeptides, we would have to protect the amino group of glycine and the carboxyl group of alanine ... 

Consider, for example, the reaction of hydrazine with a very simple dipeptide such as Gly-Ala. Hydrazine cleaves the peptide by nucleophilic attack on the carbonyl group of glycine. 

Both Gly-Ala and Ala-Gly have one acidic and one basic group. Using Table 17.2 as a guide, the expected p/ (the pH at which the dipolar forms shown in Example 17.5 will predominate for these dipeptides) is approximately 6. Gly-Ala is expected to be positively charged at pH 3. 

This process could also be applied to the synthesis of tripeptides. A Cbz-protected dipeptide (Cbz-Ala-Gly-OEt) was deprotected in flow using the H-Cube system, and using the above procedure the tripeptide Cbz-Phe-Ala-Gly-OEt was obtained in 59% overall yield and in only 6-7 h, based on the longest linear sequence from glycine. 

Dipeptides (gly-leu, ala-phe, leu-gly, ala-val)—Prepare 25 glass test tubes (13 X 100 mm) and 25 microcentrifuge tubes each containing 2 mg of one of the dipeptides. Number each of the tubes in matching sets. Keep a record of the students names and their unknown numbers. Any dipeptide can be used, provided that cysteine, tryptophan, arginine, glutamine, and asparagine are not present. 

Fig. 1. Enthalpy-entropy compensation for nonenzymatic prolyl isomerization (see Table I for literature references). 9, Proline-containing oligopeptides A, dipeptide , Gly-Gly-Lys-Phe-Pro. 1, Suc-Ala-Leu-Pro-Phe-pNA 2, Suc-Ala-Ala-Pro-Phe-pNA 3, Gly-Gly-Pro-Ala 4,N,N-dimethylacetamide 5,Suc-Ala-Trp-Pro-Phe-pNA 6, Suc-Ala-Gly-Pro-Phe-pNA 7, Gly-Pro 8, Ala-Pro 9, Val-Pro 10, His-Pro 11, Gly-Gly-Lys-Phe-Pro. Linear regression analysis of the data for compounds 1—6 yields a slope or critical temperature, T, of 232 29 K analysis of the data for compounds 7-11 yields = 212 27 K.

The dipeptides Gly-L-His, L-Ala-L-His, and L-Ala-D-His initially form 3N complexes with palladium(II), bonding through the amino, deprotonated peptide, and imidazole nitrogens. When the pH is raised above 9.5, the pyrrole proton is ionized, resulting in a 4N tetramer formation." ... 

Zinc(n), unlike copper(II) and rtickel(n), does not form very stable complexes with peptides. A study of 12 dipeptides containing the Gly, Ala, Leu, and Pro residues with zinc(II) showed that the only two species formed in detectable quantities were [ZnLH]+ and Z11L2H2. This is in contrast to copper(II) and nickel(II), in which the major species are MH iL and MH 3L. The main reason for the difference in... 

The synthesis of a specific dipeptide, such as Ala-Gly from alanine and glycine, is complicated because both amino acids have two functional groups. As a result, four products— namely, Ala-Ala, Ala-Gly, Gly-Gly, and Gly—Ala— are possible. 

FIGURE 2.29 Weight of bacterial cells produced with growth in various concentrations of serine supplement. Bacteria were grown imder a variety of conditions, with serine supplied as free serine (1) or as the dipeptides Gly-Ser (2), Ser-Ser (3), and Ser-Ala (4). (Redrawn with permission from Kihara and Snell, 1960.)... 

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