Dipeptides, simple

Aspartame, a nonnutritive sweetener marketed under the trade name Nutra-Sweet (among others), is the methyl ester of a simple dipeptide, Asp-Phe-OCH.3. 

A related palladium(O)-catalyzed epimerization of y-aziridinyl-a,P-enoates 244 was also reported by Ibuka, Ohno, Fujii, and coworkers (Scheme 2.60) [43]. Treatment of either isomer of 244 with a catalytic amount of Pd(PPh3)4 in THF yielded an equilibrated mixture in which the isomer 246 with the desired configuration predominated (246 other isomers = 85 15 to 94 6). In most cases the isomer 246 could be easily separated from the diastereomeric mixture by a simple recrystallization, and the organocopper-mediated ring-opening reaction of 246 directly afforded L,L-type (E)-alkene dipeptide isosteres 243. 

In the case of simple amino acids and dipeptides, esterification of the carboxyl groups occurs on heating in toluene with the appropriate bis(triorganotin) oxide or triorganotin hydroxide 481, 482), the water being removed azeotropically. 

OS 25] [R 4] [P 17] For dipeptide formation from the pentafluorophenyl ester of (J )-2-phenylbutyric acid and (S)-a-methylbenzylamine an extent of racemization of 4.2% was found [86]. At higher concentration (0.5 instead of 0.1 M), a higher degree of racemization was found (7.8%). This experiment also served to demonstrate monitoring of the racemization of a simple carboxylic acid used in peptide synthesis. 

Peters, D., and J. Peters. 1979. Quantum Theory of the Structure and Bonding in Proteins Part 2. The simple dipeptide. J. Mol. Struct. 53, 103-119. 

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. 

Table 1 Some naturally occurring simple cyclic dipeptides in the protist and plant kingdoms Diketopiperazine (all amino acids are in the L-configuration) Species...

DKPs are simple and easy to obtain and are quite common by-products of synthetic, spontaneous, and biological formation pathways. DKP formation has been well documented as side reactions of solid-phase and solution-phase peptide synthesis. In addition, DKPs have been shown to be decomposition products of various peptides, proteins, and other commercial pharmaceuticals. Cyclic dipeptides were found to be present in solutions of human growth hormone, bradykinin, histerlin, and solutions of agents within the classes of penicillins and cephalosporins. " DKPs are also enzymatically synthesized in several protists and in members of the plant kingdom. Hydrolysates of proteins and polypeptides often contain these compounds and they are commonly isolated from yeasts, lichens, and fungi. ... 

Modification of the amino acid residues located on the N-terminal side of Pro was shown to have a major influence on the rate of cyclic dipeptide formation. For the series of dipeptide analogues of X-Pro-/>NA, the half-lives of cyclic dipeptide formation in 0.5 molG phosphate buffer (pH 7) at 37 °C were reported as follows X = Gly 5.1 days, X = Val 2.5 days, X = Ala 1.1 days, X = /3-cyclohexylalanine 0.8 days, X = Arg 0.7 days, and X = Phe 0.5 days. Increased bulkiness of alkyl and aryl substituents have been previously shown to increase the rate of cyclization due to intramolecular reactions. This however does not seem true for the series studied by Goolcharran and Borchardt as the Ala analogue cyclized twice as fast as the bulkier analogue. From the study it is evident that simple steric bulk of substituents alone cannot be used to effectively explain the effects involved in the formation of cyclic dipeptides from various peptide precursors. 

The sections presented above provide an account of the separate topics into which translation can be divided. These act as an introduction to the current section, in which a description of the individual reactions in peptide synthesis is presented in a single diagram, i.e. a diagram that encapsulates the whole process (Figure 20.22). An analysis of each separate reaction provides a simple explanation of the interactions that are required in a sequential manner to form the various complexes in the pathway, the activities of which result in the synthesis of, initially, a dipeptide but then a growing peptide. The repetition of the formation of the complexes for each amino acid results in the synthesis of the final peptide, as dictated by the base sequence in the mRNA. 

A new interesting development has been offered by Orgel and coworkers (Leman et al., 2004) they showed that carbonyl sulfide (COS), a simple volcanic gas, brings about the formation of peptides from amino acids under mild conditions in aqueous solution, and in yields approaching 80% in minutes to hours at room temperature. Dipeptides and tripeptides were thus obtained, but in this case too the answer to the question of long chains with a regulated order of sequence remains elusive. 

The next classes of reagents developed are those for the cyclopropanation of unfunctionalized alkenes. After early attempts at getting high enantioselectivities for the cyclopropanation of /3-methylstyrene using a chiral alcohol (21), bis(iodo)methylzinc, diethylzinc, dichloromethane and a Lewis acid (equation 90) , Shi and coworkers made a major breakthrough when they found that a simple dipeptide (22) derived from valine and proline could be used (equation 91) . However, in either case, the absolute stereochemistry of the cyclopropane has not been determined. 

Complexes of other amino acids or their derivatives with cobalt(II) that have been investigated include dipeptides (120) these complexes have long been known to absorb dioxygen. For example, the mononuclear cobalt(II) complex of N, N,N", N "-diglycylethylenediaminete-traacetic acid (121) absorbs one mole of dioxygen per two moles of complex. This system has been proposed as a simple, convenient model system for the study of dioxygen complexes of cobalt(II) peptides in solution because of its relatively slow conversion to the irreversibly formed cobalt(III) dioxygen complex. 

This equation is not intended to imply a mechanism for peptide synthesis. The equilibrium position for this reaction in an aqueous solution favors the free amino acids rather than the peptide. Therefore, both biological and laboratory syntheses of peptides usually do not involve a simple splitting out of water. Since the dipeptide of Eq. 2-11 still contains reactive carboxyl and amino groups, other amino acid units can be joined by additional peptide linkages to form polypeptides. These range from short-chain oligomers to polymers of from 50 to several thousand amino acid units, the proteins.75-77... 

Nitrono) or t i[CH=N+(0 )] 1 peptides were introduced in 1987 by Grundke et al. [11 This pioneering work on simple model (nitrono) peptides has not been continued, and no (nitrono) analogue of a bioactive peptide has been reported so far. However, model (nitrono) dipeptides (e.g., 12) have been prepared in good yield (Scheme 2) by coupling an N-pro-tected a-amino aldehyde12 with the hydroxyamide terminus of an a-hydroxyamino acid derivative, 3 the synthesis of which is presented in Section 10.8.3.1. 

The synthesis of the starting aminoacyl nitrile 39 was carried out by the modified method of Lowe and Yuthavong 91,92 as shown in Scheme 19. The dipeptide derivative 43 was produced by simple chloroformate-mediated condensation of 42 with aminoacetonitrile formally derived from Gly. This example uses the TV-methoxycarbonyl protection group, presumably to avoid steric interference in the target enzyme active site. 

The simple condensation between two amino-acids to form one molecule yields a dipeptide. Polypeptides are thus large molecules of amino-acids linked together via peptide bonds. 

The most common functional templates are those of simple amino compounds 4, amino acids 5, and dipeptides 8 (Scheme 3). The simplest amino templates, the tris(ethylene amine) ammonia types 6, 7, and 9 first used in organic dendrimers, have only just begun to be applied in forming peptide dendrimers. Constrained and usual amino acids and heterocyclic compounds such as porphyrin 13, have also been reported.1691... 

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