Histidine amides

C-Methylated amino acids were prepared as follows N-Acetyl-L-tyrosine-amide, polylysine HBr, Gly-Leu, Ile-NH2, Ala-Ala, Phe-Gly-Gly, histidine amide, and cystine dimethylester dihydrochloride were methylated with iodomethane to serve as standards for the assignment of peak resonances in methylated proteins. 

N-a-Amino acids (10 mg) were typically dissolved in 200 mM, pH 10 sodium metaborate buffer (1 ml), and methylated directly by the addition of a 1 1 v/v solution (20 gl) of [ C]iodomethane in acetonitrile, with rapid mixing of the sealed biphasic mixture at 37°C for 24 h. Cystine dimethyl ester, in particular, was first converted to the diamide at pH 9.5 using ammonia. Histidine amide was first acetylated prior to reaction with iodomethane. 

The phenolic hydroxyl group of tyrosine, the imidazole moiety of histidine, and the amide groups of asparagine and glutamine are often not protected in peptide synthesis, since it is usually unnecessary. The protection of the hydroxyl group in serine and threonine (O-acetylation or O-benzylation) is not needed in the azide condensation procedure but may become important when other activation methods are used. 

A/- -toluene su1fony1)-T-phenylalanine (62), L-histidine methyl ester (63), A/-acetyl L-valine /-butyl amide (64), etc, are used as chiral addends. 

The mechanism for the lipase-catalyzed reaction of an acid derivative with a nucleophile (alcohol, amine, or thiol) is known as a serine hydrolase mechanism (Scheme 7.2). The active site of the enzyme is constituted by a catalytic triad (serine, aspartic, and histidine residues). The serine residue accepts the acyl group of the ester, leading to an acyl-enzyme activated intermediate. This acyl-enzyme intermediate reacts with the nucleophile, an amine or ammonia in this case, to yield the final amide product and leading to the free biocatalyst, which can enter again into the catalytic cycle. A histidine residue, activated by an aspartate side chain, is responsible for the proton transference necessary for the catalysis. Another important factor is that the oxyanion hole, formed by different residues, is able to stabilize the negatively charged oxygen present in both the transition state and the tetrahedral intermediate. 

Amines, amino acids, amides [1, 2] e.g. chloramphenicol, creatine, adenine, guanine histidine, phenylalanine, sphingosine... 

These complexes show considerable in vitro cytotoxic effects against various tumor cell lines [70, 71[. Moreover, the cationic complexes [Au(N,N, N")Cl[Cl are able to intercalate into ct DNA [71[. Gold(III) amidate complexes of histidine containing... 

Figure 2.12 Amidate complexes of histidine containing peptides, (19) and (20), and of amides of EDTA, (21).

The insertion of histidine in position two of the peptide chain results in the simultaneous binding of the N-terminal amine, the imidazole, and the intervening amide-N to the Ni11 ion. The major complex [NiH iL]+ with NH2,N am,Nim binding mode is pseudo-octahedral and in... 

Selective cleavage of peptides and proteins is an important procedure in biochemistry and molecular biology. The half-life for the uncatalyzed hydrolysis of amide bonds is 350 500 years at room temperature and pH 4 8. Clearly, efficient methods of cleavage are needed. Despite their great catalytic power and selectivity to sequence, proteinases have some disadvantages. Peptides 420,423,424,426 an(j proteins428 429 can be hydrolytically cleaved near histidine and methionine residues with several palladium(II) aqua complexes, often with catalytic turnover. 

With N,0 mixed donor ligands several complexes have been reported with ligands such as 4,5-dichloro-2-cyano-3,6-dione-l,4-cyclohexen-l-ol,1445 isonicotinic acid,1446 p-aminobenzoic acid,1447 alanine, histidine or histamine derivatives,1448-1450 [N(0)C(CN)2]-,1451 pyridine-carboxylate derivatives, 1452 1454 [N(pph20)2] (263),1455 bis(sulfonyl)amide derivatives,1456,1457 tris(pyridyl)-... 

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