L-Leucyl-D-phenylalanine

Acid catalyzed hydrolysis followed by the identification of D-amino acids in the hydrolysate is equally useful. To make this possible the amino acids in the mixture are acylated with an enantiomerically pure amino acid, for instance with the N-carboxyanhydride of L-leucine. In the resulting mixture of dipeptides any racemized residue is revealed by the formation of two dipeptides that are diastereoisomers of each other, for instance L-leucyl-L-phenylalanine and L-leucyl-D-phenylalanine. Since these are compounds with different physical properties they are separable and appear as a doublet on recordings of an amino acid analzyer. In recent years the conversion to diastereoisomers became unnecessary because the availability of chiral supports now permits separation of enantiomers by high pressure liquid chromatography (HPLC) and also by thin layer chromatography on plates covered with a chiral layer. 

In an attempt to clarify the relationship between gramicidin S and its bacterial action, Harris and Work (258,259,260) synthesized a series of noncyclic peptides structurally similar to those of the naturally occurring peptides. These peptides are as follows D-phenylalanyl-L-proline methyl ester, L-phenylalanyl-L-proline ethyl ester L-leucyl-n-phenylalanine methyl ester L-leucyl-D-phenylalanyl-L-proline methyl ester L-leueyl-L-phenylalanyl-L-proline ethyl ester L-ornithyl-L-Ieucyl-n-phenylalanyl-L-proline methyl ester a-(L-valyl)-DL-ornithyl-L-leucyl-D-phenylalanyl-L-proline methyl ester o -(L-valyl)-L-ornithyl-L-leucyl-D-phenylalanyl-L-proline a-(L(valyl)-DL-ornithyl-L-leucyl-L-phenylalanyl-L-proline ethyl ester a-(tosyl-L-valyl) -L-ornithyl-L-leucyl-n-phenylalanyl-L-proline methyl ester a-(tosyl-L-valyl)-L-ornithyl-L-leucyl-D-phenylalanyl-L-proline amide. 

Abe s group (Abe, 1971 Abe et al, 1970) isolated L-leucyl-D-proline lactam and L-phenylalanyl-D- and L-proline lactam from cultures in which ergokryptine and ergotamine, respectively, were the major peptide alkaloids. The time course of production of the lactams was consistent with their involvement in peptide alkaloid biosynthesis (Abe et al, 1970). The role of the lactams as precursors of the peptide alkaloids was tested by carrying out incubations with the tritium-labeled lactams. Incorporation of L-leucyl-D- and -L-proline lactam into ergokryptine plus ergokryptinine was 0.06-1.45%, and incorporation of L-phenylalanine-D- and -L-proline lactam... 

L-valyl-L-phenylalanine-2-propanol (1/1) and L-leucyl-L-phenylalanine-2-propanol (1/1) (P-form), Acta Cryst. C55, 2171-2177 d) Gorbitz, C. H. and Torgersen, E. (1999) Symmetry, pseudosymmetry and packing disorder in the alcohol solvates of L-leucyl-L-valine Acta Cryst. B55, 104-113 e) Mitra, S. N., Govindasamy, L. and Subramanian, E. (1996) L-Leucyl-L-alanine dimethyl sulfoxide solvate, Acta Cryst. C52, 2871-2873. 

The antimalarial activity of the linear coumarinolignan, grewin (18), was evaluated on cultures of Plasmodium falciparum clones D6 and W2 and it displayed weak antimalarial activity with no discernible cytotoxicity (69). Cleomiscosin A (9) and aquillochin (7), isolated as major constitutents from the heartwood of Acer nikoense, exhibited moderately potent vasorelaxant effects in the rat aorta using nor-epinephrine-stimulated and high K" -depolarized preparations (18). (7 S,8 S)-4 -0-Methyl-cleomiscosin D (29) and cleomiscosin D (11), isolated from Zan-thoxylum avicennae, were found to inhibit superoxide anion generation by human neutrophils in response to formyl-L-methionyl-L-leucyl-L-phenylalanine/cytochlasin B (52). 

Lee TH, Horton CE, Kyan-Aung U, Haskard D, Crea AE, Spur BW (1989) Lipoxin A4 and lipoxin B4 inhibit chemotactic responses of human neutrophils stimulated by leukotriene B4 and N-formyl-L-methionyl-L-leucyl-L-phenylalanine. CUn Sci (Lond) 77 195-203... 

The L-phenylalanine-L-proline lactam (137), which has been found to be present in C. purpurea cultures, serves as a precursor for ergotamine (133). This result mirrors the derivation of ergocryptine/ergocryptinine (134) from the L-leucyl-L-proline lactam (136).A pointer for ergotamine (133) biosynthesis is the clear implication of D-lysergyl-L-valine (138) in the biosynthesis 01(134)." However, lysergylalanine has been found to be a non-intact precursor of ergotamine. 

Volatile peptide derivatives, for instance trifluoroacetyl-L-valyl-L-valine methyl ester or benzyloxycarbonyl-L-leucyl-L-phenylalanyl-L-valine tert.butyl ester can be separated from their diastereoisomers that contain a D-residue by vapor phase chromatography. Also, through the examination of nmr spectra of relatively simple peptides the extent of racemization that occured during their preparation can be determined without separation of the diastereoisomers, because the difference in the chemical shifts of some selected resonances is sufficient for integration. Thus the areas under the well separated peaks of the alanine methyl protons in acetyl-L-phenylalanyl-L-alanine methyl ester and in acetyl-D-phenylalanyl-L-alanine methyl ester can be integrated and the values used to determine the extent of racemization of the phenylalanine residue during coupling. 

McCall, C. E., Bass, D. A., DeChatelet, L. R., Link, A. S. J., Mann, M. (1979). In vitro responses of human neutrophils to N-formyl-methionyl-leucyl-phenylalanine correlation with effects of acute bacterial infection. J. Infect. Dis. 140,277-86. 

Marasco, W. A., Phan, S. H., Krutzsch, H., Showell, H. J., Feltner, D. E., Nairn, R., Becker, E. L., and Ward, P. A. (1984). Purification and identification of formyl-methionyl-leucyl-phenylalanine as the m or peptide neutrophil chemotactic factor produced by Escherichia coli. J. Biol. Chem. 259, 5430-5439. 

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