N- -!,-methyl histidine

R = ch3 N(n)-Methyl-histidin [5-(2-Amino-2-carboxy-ethyt)-1-melhyl-imidazol 75%... 

The enzyme contains five posttranslationally modified amino acids near the active site N-methyl-histidine, 5-methylarginine, 2-methylglutamine, 2-methyl-cysteine, and thioglycine in a thiopeptide bond. The latter may be the site of radical formation.4583 13... 

Anserine P-alanyl-N -methyl-histidine Vertebrate skeletal muscles, heart, brain 1929... 

Ophidine p-alanyl-N -methyl-histidine Snake, dolphin and whale musculature 1939... 

Homoanserine y-aminobutyryl-N -methyl- histidine Cardiac muscle and brain 1969... 

N-acety 1-methyl-histidine N-acetyl-N -methyl-histidine Cardiac muscle and brain 1988... 

N -Acetyl-anserine N-acetyl-p-alanyl- N -methyl-histidine Heart muscle 1988... 

Homocamosinosis. This disease is accompanied with pronounced increase of homocamosine level in brain and cerebrospinal liquid as well as camosine in urea with simultaneous disability to metabolize anserine into N -methyl-histidine (see [107]). Normal level of camosine and homocamosine is exceeded 20 and more times and this is accompanied with apparent neurological deficit. At the same time, relatives of the patients can get similar shifts in dipeptides metabolism with no neurological symptomatic. The cause of such disorder of metabolism in patients with homocamosinosis is that camosine splitting enzyme, carnosinase is mainly present in the inactive form [109,110],... 

In contrast to the case of tryptophan the photoreactions with tyrosine and histidine probably involve hydrogen atom transfer as the primary step. There are several indications for this. First, 0-methylated tyrosine (p-methoxy phenylalanine) did not show any photo-CIDNP effect and its reactivity as a photo-reductant towards flavins is strongly reduced (19). Similarly, 1-N-methyl histidine is not polarized at high pH (> 7.5), when no abstractable hydrogen is present. Secondly, in the protein ribonuclease A, which has a well known 3-dimensional structure, the residues Tyr 92 and His 105 have exposed rings, but their OH and NH protons are hydrogen bonded to backbone carbonyl groups. 

Saundersoa C.L Leslie, S. (1983). N -methyl histidine excretion by poultry not all species exaete N -methyl histidine quantitatively. Br. ]. Nutr., 50, 691-700. 

Saundersoa C.L. Whitehead, C.C. (1987). N Methyl histidine excretion and [U- C] amino acid oxidation in fully fed chickens from two lines for high and low body fat contents. Comp. Biochem. Physiol, 86B, 419-22. 

Similar results were obtained in the polymerization of in-situ CDI-activated D-or L-Phe with I--methyl-histidine (M His) or L-N -methyl-histidine (M His), where oligopeptides of up to 10 residues were formed. 

This was confirmed in a subsequent work of Miller and coworker where a series of octapeptides containing N-terminal n-methyl histidine (Pmh) was developed (Figure 5.9) [31]. 

Lysine is the most common site for N-methylation, but methylation can also occur on arginine, histidine, glutamine, and asparagine. The enzymes responsible for N-methylation are known as N-methyltransferases aided with SAM as a cosubstrate. All forms of methylation share the same mechanism the nucleophilic amino acid side chain attacks the electrophilic methyl group of SAM and releases S-adenosylhomocysteine (SAH) (Scheme 7). 

Durch dasselbe Reaktionsprinzip kann auch Histidin-methylester iiber die N(a), N(t)-Diben-zoyl-Verbindung mit Trimethyl- bzw. Triethyl-oxonium-tetrafluoroborat zu N(n)-Methyl- bzw. N(n)-Ethyl-histidin (nach Abspaltung der Schutzgruppen und Esterhydrolyse) alkyliert werden882. 

Belokon et al. have published a somewhat intricate protocol for the N -methylation of a histidine isomer, itself an imidazolium derivatised a-amino acid [158] (see Chapter 6). The amino group can be N-boc protected and the resulting imidazolium salt reacted with silver(I) oxide to yield the corresponding silver(l) carbene complex. The functional groups in the wingtip group... 

Protein ( histidine ) Methyltransferase. An enzyme which methylates histidine in proteins to give primarily 3-methylhistidine residues has been observed in myofibrillar protein and in the sarcoplasmic fraction of muscle homogenates (218). S-Adenosyl-L-methionine serves as the methyl donor for the enzyme. The enzyme has not been solubilized and purified. Very little is known about the substrate specificity of protein-(histidine) methyltransferase. Actins from a wide variety of species consistently contain one 3-N-methylhistidine residue per molecule (191, 219). It appears that myosin from white muscle contains two residues of 3-N-methylhistidine (one residue per heavy chain), whereas myosin from red muscle contains no 3-N-methylhistidine (220). The amino acid sequence around the methylated residue of rabbit skeletal muscle is (221) ... 

In an attempt to improve the inhibition kinetics, a pepticinnamin E library was synthesized to explore the chemical space of the natural product7 Three types of modifications were investigated changes to the N- and C-terminal substituents on the backbone, changes in N-methylation status, and the addition of an N-terminal histidine residue to form an interaction with the active site zinc atom. The inclusion of a histidine residue at the N-terminal peptide position proved favorable and modulation of the N-terminal substituent (i.e., the farnesyl pyrophosphate mimic) proved important for inhibition. Several of the compounds from the library were shown to induce apoptosis in MDCK-f3 tumor cells at concentrations of 100 pmol 1 however, in the case of only one compound could apoptosis be linked to FT inhibition. 

Amino acid esters may coordinate as a monodentate (amino N) or as a bidentate (N,0) ligand. In the latter case (17) significant polarization of the ester bond results which is of likely importance in the reaction mechanism (Scheme 6). Alternatively, hydroxide attack at the metal centre may occur (equation 15). Hydroxide ion rather than water is the predominant nucleophile, even at pH 5. Direct evidence for metal-ester bond formation comes from isolated Co" complexes which contain such a bond. Rate enhancements, compared to the free amino acids, are often of the order of lO -lO . For methyl histidinate, however, rate enhancement by Cu" is only of the order of265 this is ascribed to there being no Cu-ester bond formation. The order of decreasing reactivity in this study was established as being CuE " > Ni > CuE > NiE " > EH" > CuEA > CuEOH > NiEA > E, where E is L-HisOMe and A is L-HisO . The relative effectiveness of protons and metal ions as catalysts has been discussed by Martin. ... 

Friedman, M., and Gumbmann, M. R. (1979). Biological availability of epsilon-N-methyl-L-lysine, 1-N-methyl-L-histidine, and 3-N-methyl-L-histidine in mice. Nutrition Reports International,... 

MOLECULAR DESIGN THEORETICAL AND SOLUTION STUDIES ON COPPER(II) COMPLEX OF GLYCYLGLYCYL-L-HISTIDINE-N-METHYL AMIDE,... 

Conformation of glycylglycyl-L-histidine-N-methyl amide may be represented by a set of torsional angles, < i, ( 2 2 J d described about the... 

Fig. 5. Conformational energy surface of glycylglycyl-L-histidine-N-methyl amide-Cu(II) complex as a function of torsional angles and x ( i=—80°, y/%=—2(f, < 2 = — 180°, v 3=—20°) in kcal mole relative to the global minimum marked x. A, B, C and D are the conformations satisfying the constraint, viz. inter-nitrogen distances suitable for forming a square planar complex.

A perspective of the minimum energy conformation of the complex is shown in Figure 6. We observe from theoretical studies that the Cu(II) atom prefers a square planar environment. Detailed account of our study and a comparison of conformations of the synthetic molecule glycylglycyl-L-histidine-N-methyl amide with the natural analogue L-aspartyl-L-alanly-L-histidyl-N-methyl amide will be presented elsewhere. 

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