P-Alanyl dipeptides

P-Alanine, a metabolite of cysteine (Figure 34-9), is present in coenzyme A and as P-alanyl dipeptides, principally carnosine (see below). Mammalian tissues form P-alanine from cytosine (Figure 34-9), carnosine, and anserine (Figure 31-2). Mammalian tissues transami-nate P-alanine, forming malonate semialdehyde. Body fluid and tissue levels of P-alanine, taurine, and... 

The P-alanyl dipeptides carnosine and anserine (A -methylcarnosine) (Figure 31-2) activate myosin ATPase, chelate copper, and enhance copper uptake. P-Alanyl-imidazole buffers the pH of anaerobically contracting skeletal muscle. Biosynthesis of carnosine is catalyzed by carnosine synthetase in a two-stage reaction that involves initial formation of an enzyme-bound acyl-adenylate of P-alanine and subsequent transfer of the P-alanyl moiety to L-histidine. 

L-Carnosine (P-alanyl-L-histidine) [305-84-0] M 226.2, m 258-260 (dec), 260 (capillary tube), 262 (dec), [a] +20,5 (c 1.5, H2O), pKf 2.64, pKf 6.83, pKf 9.51. Likely impurities are histidine and P-alanine. Crystallise L-carnosine from water by adding EtOH in excess. RecrystaUise it from aqueous EtOH by slow addition of EtOH to a strong aqueous solution of the dipeptide. Its... 

Addison, J. M., Matthews, D. M., and Burston, D., 1974, Evidence for active transport of the dipeptide camosine (P-alanyl-L-histidrne) by hamsterjejunum in vitro, Clin. Sci. Mol Med. 46 707-714. 

Camosine (P-alanyl-L-histidine) and anserine (P-alanyl-l-methyl-L-histidine) are present in high levels in the muscle and brain of mammalian and avian species (Tamaki et ai, 1976 Biffo et ai, 1990). They are recognized as antioxidants (Kohen et al, 1988). Camosine is synthesized from P-alanine (P-Ala) and histidine, and anserine is mainly formed from camosine by a methylation reaction (Boldyrev and Severin 1990). In the present study, whether dietary P-Ala could increase these dipeptide levels of the brain and breast muscle was investigated in chickens. 

FIGURE 2.17 Anserine (AA/3-alanyl-3-methyl-L-hisddine) is an important dipeptide buffer in the maintenance of intracellular pH in some tissues. The structure shown is the predominant ionic species at pH 7. p. i (COOH)... 

Purification of some enzymes participating in the biosynthesis of glycopeptide cell-wall precursors has also been achieved. Examples include preparation of the enzymes necessary for synthesis of the enol ether 38 (see Section 11,6, p. 328),152-153-450 reduction of the enol ether to the muramic acid derivative,152-450,451 and the addition to the latter of amino acids452-456 or the dipeptide D-alanyl-D-alanine.160-457-458... 

Figure 5 Inhibition of [ H]-cefadroxil uptake into Caco-2 cells by stereoisomers of alanyl peptides and selected P-lactam antibiotics. In addition, influx inhibition by the dipeptides glycyl-sarcosine (Gly-Sar) and glycyl-glutamine (Gly-Gln) and the P-lactams, amoxicillin and benzylpenicillin, is presented. Uptake of 1 mM cefadroxil into Caco-2 cells was measured at apical buffer pH 6.5 for 30 min at 37°C in the absence (control) or presence of lOmM of the inhibitors. The aminopeptidase inhibitor, amasatin, was present at a concentration of 100 pM in each experiment. Values are expressed as the mean SD of 3-6 monolayers. Hatched columns ( / ) no significant inhibition open columns 50% inhibition back hatched columns ( ) 60% inhibition. (Adapted from Ref. 16.)... 

The synthesis of N-acetyl-P-D-glucosaminyl-(l- 4)-N-acetyl-mur-amyl-dipeptide according to various synthetic (82—84) and hemi-synthetic (85) procedures has been described, and, also, the synthesis of one of its isomers 0-(N-acetyl-P-muramyl-L-alanyl-D-isoglutamine)-(l- 4)-N-acetyl-D-glucosamine (90) (86). 

Chedid, L., M. Parant, F. Parant, F. Audibert, P. Lefrancier, J. Choay, and M. Sela Enhancement of certain biological activities of muramyl dipeptide derivatives after conjugation to a multi-poly-(DL-alanyl)-poly-(L-lysine) carrier. Proc. Natl. Acad. Sci. USA 76, 6557 (1979). 

N -[ N-P -Acetylmuramoyl) -L-alanyl]-D-a-glutamine, 9CI. N-Acetylmuramyl-L-alanyl-D-isoglutamine. Muramyl dipeptide. MDP... 

Levine The dipeptide conformations we have observed using the lanthanide probes in aqueous solution have all been fairly extended structures with 0, W values of —60° and +140°. We note however that in the case of L-alanyl L-alanyl L-alanine the conformation adopted approaches that of a simple helix (Figure 6). We do not find that the preferred conformation of the L-alanyl L-alanine dipeptide is either the C5 or the C form in aqueous solution. We have not investigated the peptide conformations in non-aqueous solvents using the lanthanides as n.m.r. probes but such systems are reviewed by B. C. Mayo Chem. Soc. Rev. 2 (1) p. 49 (1973). The conformations of the diastereomers of phenylalanyl alanine in chloroform confirm the stereochemistry of the 7-member H-bonded ring (Martinelli, Honiberg, and Sternson Tetrahedron 29, p. 1671, (1973)). 

The alanine tripeptide, alanyl isoleucine, and isoleucyl alanine were obtained at 98 % purity. Tri-L-alanine was recrystallized in different ways to produce two different crystalline forms. Following the recipes of Hempel, Camerman and Camerman (29), platelet-type crystals of the parallel p-sheet form were obtained and needle-shaped crystals of the anti-parallel P-sheet form were produced. The crystalline dipeptides were used as received. 

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