Dipeptides, imidazole

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. 

Another -activation of amino acids for peptide synthesis is achieved by preparing sulfenamides from sulfenylimidazoles. A sulfenylimidazole is formed in situ from the sulfenyl chloride (prepared from the disulfide and chlorine) and imidazole, which reacts further with an amino acid ester to give a sulfenamide in high yield. Conversion of such sulfenamides with IV-acyl amino acids by means of triphenylphosphine affords dipeptides with racemization of less than 0.5%.[481... 

Dunnet, M. and Harris, R. C. (1997). High-performance liquid chromatographic determination of imidazole dipeptides, histidine, 1-methylhistidine and 3-methylhistidine in... 

Tsubone, S., Yashikawa, N., Okada, S., and Abe, U. (2007). Purification and characterization of a novel imidazole dipeptide synthetase from the musde of the Japanese eel Anguilla japonica. Comp. Biochem. Physiol. B Biochem. Mol. Biol. 146,560-567. 

The preparation of an imidazole-pyrrole dipeptide segment for DNA binding studies is shown in Scheme 3[10 and described in Section 11.2.1. 

Histidine-containing dipeptides show a more complex chemistry than found for the dipeptides discussed above. Three complexes of monoperoxovanadate are formed, two of which have the characteristics of the complexes described above. The clearly obvious difference of the third type of complex from the others, as exemplified in Table 6.5, is that they have a pKa. The pKa values that have been measured are significantly different from that of the imidazole of the histidine... 

Likewise, oxazoles have been used as protecting-activating groups for carboxylic acids [57], and imidazoles have been transformed to amino acid diamides and dipeptides (Sch. 36) [54a],... 

The highly unstable endoperoxides of imidazoles, sometime spectroscopically detected [81a], rearrange to dioxetanes or hydroperoxides or rapidly fragment or polymerize so that from the synthetic perspective, the reaction has a poor scope [54,67,81]. One interesting application has been pointed out by Lipshutz as a general asymmetric synthesis of TV-protected amino acids/dipeptides via appropriately substituted imidazoles (Sch. 48) [82],... 

Several histidine-containing cyclic dipeptides catalyse phenolic acetates (65). Cyelo(Gly-L-His), cydo(L-Leu-L-His) and cyclo(D-Leu-L-His) have almost the same pK value of their imidazole moieties as that of imidazole. Nevertheless, catalytic activities of the former two cyclic dipeptides are less than that of imidazole and the latter has an activity of 20-times that of imidazole. This was also explained by showing that there are considerable steric hindrances influencing the catalysis and that the latter has a remarkably effective hydrophobic interaction which exceeds the hindrance. 

From the comparative experiments in DjO the catalysis by the cyclic dipeptides was confirmed to be nucleophilic, which is the same as the imidazole catalysis. It is seen in Table 16 that in the hydrolysis of PNPA kc for the cyclic peptides is onfy 1/10-1/5 as much as that for imidazole. The lower reactivity of the cyclic dipeptides is explained partly in terms of the lower pKj values and partly because of the larger steric hindrance for the nucleophilic reaction. Only when the pattern of the substrate binding—intramolecular catalysis of the cyclic peptides excels the decrease of basicity and the increase of steric hindrance, an enhanced catalysis by the cyclic dipeptides is possible. With regard to an increase of reactivity was expected for the hydro-phobic interactions by a sli tly larger acyl chain and for the aromatic-amide interaction (see Sections 3.3 and 3.6) between the p-phenyl group of the substrate and... 

On the basis of the NMR data, they depicted the most plausible conformation of the cyclic dipeptide as follows. In cyclo(L-Leu-L-His) 18, tire imidazole group is diielded by the isobutyl side drain and the diketopiperazine ring, so that its reaction with substrate is less favorable. In contrast, the two pendent groups are ideally situated in cycIo(D-Leu-L-His) i 7 for interaction with long-chain wbstrates. 

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