Alanyl-leucine

It was first shown byE. Fischer, in 1894, that enzymes were specific in their action thus maltase acts only upon a-glucosides and emulsin only upon /3-glucosides. Later, he found that trypsin acted asymmetrically upon inactive polypeptides, e.g., alanyl-leucine was hydrolysed in such a way that only the compound composed of d-alanineand I-leucine, the natural isomers, was split up into its constituents, whereas the compound composed of 1-alanine and d-leucine was unattacked. Again, inactive leucine ester was found by Warbui to be only partially hydrolysed by trypsin he obtained 1-leucine and d-leucine ester. 

Concerning the nomenclature of the two compounds where they have been isolated, the more insoluble is called the A compound and the more soluble the B compound. It has been possible to determine by the action of trypsin, which only hydrolyses the compound containing the naturally occurring amino acids, what combinations are present in them thus, as alanyl-leucine A was hydrolysed by trypsin it must contain d-alanyl-l-leucine, and the two compounds must therefore be... 

The number of isomers of diketopiperazines containing two molecules of different amino acids is greater than when the two amino acids in the molecule are the same. It can be calculated from the number of asymmetric carbon atoms in the molecule just as in the open chain compounds thus alanyl-leucine anhydride can exist in four optically active forms and two racemic forms —... 

The same diketopiperazines are obtainable either from the dipep-tidcs alanyl-leucine or from the dipeptides leucyl-alanine, so that in fact the number of isomers of a diketopiperazine composed of two different amino acids is less than those of the i.somers of the dipeptide composed of the same two amino acids. 

Glycyl-alanine, NHj. CHg. CO — NH, CH(CHj). COOH, was not hydrolysed, but the isomeric alanyl-glycine, NHj.CHCCHa). CO — NH. CHg. COOH, was hydrolysed again, alanyl-leucine A was hydrolysed, but not leucy 1-alanine. 

The compounds marked with an asterisk are racemic and their hydrolysis was effected asymmetrically, only that portion of the molecule containing the natural stereoisomer being attacked. This explained the difference between alanyl-leucine A and alanyl-leucine B the former probably consisted of d-alanyl-l-leucine -l- 1-alanyl-d-leucine, the first of which contains the natural stereoisomers upon which the hydrolysis depends the latter would consist of d-alanyl-d-leucine1-alanyl-l-leucine. The later experiments of 1907 proved this supposition. It is more noticeable in the case of leucyl-leucine, which must have been... 

E. Fischer und O. Warburg. Synthese von Polypeptiden. XI. 3. Olycyl-leucine, Alanyl-leucin, Leucyt-alanin, Glycyl-alanyl-leucin, und aktives Alanyl-glycin. Annalen,... 

In 1984 a third phosphinothricin-produdng microorganism was discovered and described as Kitasatospora phosalacinea (syn. Strq>tomyces phosalacineus) which produces phosphinothricyl alanyl-leucine (phosaladne) [16,17]. 

Di-phosphinothridn 307 L-phosphinothricin 303, 307 phosphinothricyl alanyl-leucine 307 2-phosphoglycolate 303 phoxim 760 phthalide 973 Pico 206, 1222... 

CuHnN40s Immylgfycyl-alanyl-leucin Athyl amid 4 II 2. 

Z-Phe Leu-OMc[L-Leucine, A7-[A7-[(phonylmethoxy)-curbonyl]-L-pheny]alanyl]-, methyl ester] B 90%... 

N-[N-(benzyloxycarbonyl)-L-aspart-l-oyl-(L-alanyl-L-threonyl-L-leucine p-nitrobenzyl ester)-4-oyl]-... 

Still using heterogeneous gramicidin, Synge24 isolated the D-leucylglycine, L-alanyl-D-valine and L-alanyl-D-leucine from partial hydrolysates of gramicidin. He also had less conclusive evidence for the tripeptides alanyl-valylleucine or alanylleucylvaline. 

FIGURE 1.19 X-ray crystal structures of selector-selectand complexes (ion-pairs) (a) O-9-(P-chloro-fert-butylcarbamoyl)quinine with iV-(3,5-dinitrobenzoyl)-(5)-leucine, (b) tbe pseudoenantiomeric complex of 0-9-( 3-cbloro-tert-butylcarbamoyl)quinidine with N-(3,5-dinitrobenzoyl)-(i )-leucine, (c) 0-9-( 3-cbloro-terf-butylcarbamoyl)quinine with N-(3,5-dinitrobenzoyl)-(5)-alanyl-(5)-alanine, and (d) comparison of tbe complexes of (a) and (c). Most hydrogens have been omitted for the purpose of clarity. (Reprinted from C. Czerwenka et al., Anal. Chem., 74 5658 (2002). With permission.)... 

Cyclosporine A Cyclosporine A, [R-[R, R -(E)]]-cyclo-(L-alanyl-D-alanyl-iV-methyl-L-leucyl-iV-methyl-L-leucyl-A-methyl-L-valyl-3-hydroxy-iV,4-dimethyl-L-2-amino-6-octenoyl-L-a-aminobutyryl-A-methylglycyl-iV-methyl-L-leucyl-L-valyl-iV-methyl-L-leucine) (31.2.2), is extracted from a cultural liquid of products of the vital activity of the mushroom Tolypocladium inflatum [14-17], and which is also proposed to obtain synthetically [18-20]. 

Although CDI was applied as early as 1972 as reagent for the esterification of starch and dextran, it has only scarcely been used up to now. Its renaissance during the last few years may be due to the fact that it became an affordable commercially available product. Among the first attempts for the esterification of polysaccharides via CDI is the binding of amino acids onto dextran. Besides CDI, -(thiocarbony diimidazole can be utilised to obtain the corresponding imidazolide [198]. The amino acids bound via this path are glycine, L-leucine, L-phenylalanine, L-histidine and L-alanyl-L-histidine. They are protected with N-trifluoroacetyl, N-benzyloxycarbonyl... 

Bonds formed by the other amino acids do not appear to be hydrolyzed as readily as those of the aromatic amino acids and leucine. The large number of alanyl bonds which were hydrolyzed in the proteins given in Table IX suggest that this residue also forms bonds that are split easily. 

Only a small number of the alanyl bonds, however, are hydrolyzed. In a-chains only three of the twenty bonds formed by the carboxyl groups of alanine are cleaved, whereas in /3-chains only four of the fifteen alanyl bonds are cleaved. Thus, the bonds formed by carboxyl groups of amino acids other than leucine and the aromatic amino acids may be split because they form the peptide linkage with amino groups of the aromatic residues or leucine. An explanation is lacking for the hydrolysis of bonds such as -Asp-Pro-, -Arg-Ileu-, -Gly-Arg-, and -Ser-Asp-. Cleavage of bonds of this type has not been observed frequently and cannot be expected to be encountered often. 

Inhib. abbrev. DTT = dithioghreitol E64D = epoxysuccinyl-L-leucyl-amido-3-methyl-butane ethyl ester EDTA = ethylene-diamine-tetra-acetic acid EGTA = ethylen-glycol-tetra-acetic acid LHVS = morpholinurea-leucine-homophenyl-alanine-vinylsulfone-phenyl NEM = N-ethyl-maleimide PAI = plasminogen activator inhib. PMSF = phenil-methyl-sulfonil fluoride SBTl = soybean trypsin inhib. TIMP = tissue inhib. of metalloproteinases TPCK = tosyl-L-phenyl-alanyl-chloro-methane Al.so termed stephins. 

These enzymes have been linked here because they have some common applications in diagnostic enzymology. Alanine aminopeptidase (AAP) and leucyl arylamidase (LAAP) hydrolyze the N-terminal amino acids and some amino amides the enzymes respectively hydrolyze leucyl- and alanyl-4-nitroanilide substrates. These enzymes occur in microsomes and are also membrane bound they have been used in studies of both hepatotoxicity and nephrotoxicity. They should not be confused with cytosolic leucine aminopeptidase (LAP) this enzyme is an aminopeptidase that hydrolyzes N-amino acid residues of proteins, in particular those with an N-terminal 1-leucine, where l-leucyl-(3-napthylamide is commonly used as substrate. Urinary alanine aminopeptidase is a useful marker of nephrotoxicity (Jung and Scholz 1980). 

By the careful hydrolysis of certain proteins, peptids of definite structure have been obtained. From silk-fibroin have been obtained the anhydrides of glycyl-d-alanine and glycyl-Z-tyrosine, and a tetrapeptid which consists of two molecules of glycine, one molecule of alanine, and one molecule of tyrosine. It has been shown that the products of the partial hydrolysis of elastin contain cZ-alanyl-Z-leucine, alanyl-proline anhydride, and glycyl-valine anhydride. Other peptids have been obtained from gliadin and casein. 

In the same way alanyl-alanine and alanyl-alanine ester, which yielded caibethoxyl-alanyl-alanine ester when treated with ethylchloro-carbonate, can be obtained from alanine anhydride, and leucyl-leucine from leucine anhydride or leucinimide, which was first obtained in 1849 regarded as occurring in the protein molecule, by... 

Optically Active. Glycyl-l-tyrosine. Glycyl-d-alanine. Glycyl-d-tryptophane. Glycyl-l-phenylalanine. Glycyl-3, 5-diiodo-l-tyrosine. dl-Alanyl-d-alanine. 1-AlanyI-glycine. d-Alanyl-d-alanine. d-AIanyl-l-leucine. d-Alanyl-d-tryptophane. 

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