Methylated amino acid residues

Cyclosporin A contains II amino acids, joined in a cyclic strncture by peptide bonds. The structure is also stabilized by intramolecular hydrogen bonds. Only two of the amino acids, i.e. alanine and valine, are typical of proteins. The compound contains several A-methylated amino acid residues, together with the even less common L-a-aminobutyric acid and an Ai-methylated butenylmethylthreonine. There is one o-amino acid, i.e. o-alanine, and the assembly of the polypeptide chain is known to start from this residue. Many of the other natural cyclosporin structures differ only with respect to a single amino acid (the a-aminobutyric acid residue) or the number of amino acids that have the extra Ai-methyl group. 

Tables 10 and 11 summarize the solution and sohd-phase synthesis, respectively, of many peptides that contain at least two consecutive N-methyl amino acid residues.

CsA is a cyclic undecapeptide consisting completely of hydrophobic amino acids, as shown in Figure 1.8 [37]. Additional structural features are a threonine-derived butenyl-containing amino acid derivative as well as six N-methylated amino acid residues. In addition to reducing the proteolytic degradation rate and increasing the... 

The various methylated amino acid residues are widely distributed in nature, and the lysine and arginine derivatives were present in every tissue examined except Eubacterium, which did not contain any methylated arginine (195). These derivatives are found in highly specialized... 

Table VII. Methylated Amino Acid Residues Occurring in Proteins...

DNA-JV-methyladenine or 5-rrredr.ylcytDsme Methylated tRNA bases - Methylnicotinamide Methylated amino acid residues... 

These methylated amino acid residues are present ubiquitously in nature, ranging from eukaryotic to prokaryotic organisms (1), and their presence are extremely selective occurring in highly spe-cialyzed proteins such as histone, flagella protein, myosin, actin, ribosomal proteins, opsin, fungal and plant cytochrome calmodulin and myelin basic protein. The methylation of these proteins... 

Transfer RNA (tRNA) serves as a carrier of amino acid residues for protein synthesis. Transfer RNA molecules also fold into a characteristic secondary structure (marginal figure). The amino acid is attached as an aminoacyl ester to the 3 -terminus of the tRNA. Aminoacyl-tRNAs are the substrates for protein biosynthesis. The tRNAs are the smallest RNAs (size range—23 to 30 kD) and contain 73 to 94 residues, a substantial number of which are methylated or otherwise unusually modified. Transfer RNA derives its name from its role as the carrier of amino acids during the process of protein synthesis (see Chapters 32 and 33). Each of the 20 amino acids of proteins has at least one unique tRNA species dedicated to chauffeuring its delivery to ribosomes for insertion into growing polypeptide chains, and some amino acids are served by several tRNAs. For example, five different tRNAs act in the transfer of leucine into... 

In the spectrum of fully reductively [ C] methylated glycophorin A, the resonance at 42.8 p.p.m. must correspond to the N, N -di[ C]methylated, N-terminal amino acid residue. The ratio of the integrated intensities of the N, N -di[ C]methylLeu resonance to the N, N -di[ C]methyllysine resonances is 5 1, as expected. The integration values determined were valid, because the recycle times of spectra in Figs. 3B, 3C, and 3D were twice the spin-lattice relaxation-times (Tj values) of those of the di[ C]methyl carbon atoms, and also because the n.O.e. values of the N, N -di[ C]methyl and N, N -di[ C]methyl carbon atoms were equivalent. ... 

Fig. 9 Correlation of (A) the second order rate constants (k2 = kcatIKM) and (B) the transition stabilization (pATS) with the hydrophobicity (it) of the substituent of the amino acid residue for the cleavage of /V-acetylamino acid methyl esters by a-chymotrypsin. The open symbols are for the points for two branched residues (valine and isoleucine). Data from Table A6.8.

To verify such a steric effect a quantitative structure-property relationship study (QSPR) on a series of distinct solute-selector pairs, namely various DNB-amino acid/quinine carbamate CSPpairs with different carbamate residues (Rso) and distinct amino acid residues (Rsa), has been set up [59], To provide a quantitative measure of the effect of the steric bulkiness on the separation factors within this solute-selector series, a-values were correlated by multiple linear and nonlinear regression analysis with the Taft s steric parameter Es that represents a quantitative estimation of the steric bulkiness of a substituent (Note s,sa indicates the independent variable describing the bulkiness of the amino acid residue and i s.so that of the carbamate residue). For example, the steric bulkiness increases in the order methyl < ethyl < n-propyl < n-butyl < i-propyl < cyclohexyl < -butyl < iec.-butyl < t-butyl < 1-adamantyl < phenyl < trityl and simultaneously, the s drops from -1.24 to -6.03. In other words, the smaller the Es, the more bulky is the substituent. The obtained QSPR equation reads as follows ... 

---