Aromatic side chain

Site of chymotrypsin catalyzed hydrolysis when R is an aromatic side chain... 

Even though these enzymes have no absolute specificity, many of them show a preference for a particular side chain before the scissile bond as seen from the amino end of the polypeptide chain. The preference of chymotrypsin to cleave after large aromatic side chains and of trypsin to cleave after Lys or Arg side chains is exploited when these enzymes are used to produce peptides suitable for amino acid sequence determination and fingerprinting. In each case, the preferred side chain is oriented so as to fit into a pocket of the enzyme called the specificity pocket. 

This is nicely illustrated by members of the chymotrypsin superfamily the enzymes chymotrypsin, trypsin, and elastase have very similar three-dimensional structures but different specificity. They preferentially cleave adjacent to bulky aromatic side chains, positively charged side chains, and small uncharged side chains, respectively. Three residues, numbers 189, 216, and 226, are responsible for these preferences (Figure 11.11). Residues 216... 

Figure 11.11 Schematic diagrams of the specificity pockets of chymotrypsin, trypsin and elastase, illustrating the preference for a side chain adjacent to the scisslle bond In polypeptide substrates. Chymotrypsin prefers aromatic side chains and trypsin prefers positively charged side chains that can interact with Asp 189 at the bottom of the specificity pocket. The pocket is blocked in elastase, which therefore prefers small uncharged side chains.

Hydrodealkylation. Hydrodealkylation is a cracking reaction of an aromatic side chain in presence of hydrogen. Like hydrocracking, the... 

Figure 6.14 Enzymatic side chain cleavage of penicillins. 6-Aminopenicillanic acid, a valuable intermediate for the production of various semi-synthetic penicillins, can be obtained through enzyme-mediated hydrolysis of the phenylacety group of penicillin G or the phenoxyacetyl group of penicillin V. The active site of the enzyme recognises the aromatic side chain and the amide linkage, rather than the penidllin nucleus. Chemical entitles other than penicillins are therefore often good substrates, as long as they contain the aromatic acetamide moiety.

Chymotrypsin-like proteinases are serine proteinases that recognize pqDtide residues with aromatic side chains (phyenylalanyl or tyrosyl residues) and that effect hydrolysis of the polypeptide chain on the carboxy-terminal side of these residues. Examples of chymotrypsin-like proteinases are chymotrypsin and cathepsin-G. 

Titov claims that the free radical mechanism applies for nitration of aliphatic hydrocarbons, of aromatic side chains, of olefins, and of aromatic ring carbons, if irf the latter case the nitrating agent is ca 60—70% nitric acid that is free of nitrous acid, or even more dil acid if oxides of nitrogen are present... 

If a target aminodicarboxyl units bears an aryl group in one of its side chains, retrosynthetic analysis indicates that a bromoamide synthon 12, bearing an aliphatic side-chain, should react with a nucleophilic partner carrying the aromatic side chain. In the alternative bromoamide 21, HBr elimination to cinnamic derivatives competes with the desired bromine substitution. 

CD and NMR Studies of a Helical Peptoid Pentamer with a-Chiral Aromatic Side Chains... 

A peptoid pentamer of five poro-substituted (S)-N-(l-phenylethyl)glycine monomers, which exhibits the characteristic a-helix-like CD spectrum described above, was further analyzed by 2D-NMR [42]. Although this pentamer has a dynamic structure and adopts a family of conformations in methanol solution, 50-60% of the population exists as a right-handed helical conformer, containing all cis-amide bonds (in agreement with modeling studies [3]), with about three residues per turn and a pitch of 6 A. Minor families of conformational isomers arise from cis/trans-amide bond isomerization. Since many peptoid sequences with chiral aromatic side chains share similar CD characteristics with this helical pentamer, the type of CD spectrum described above can be considered to be indicative of the formation of this class of peptoid helix in general. 

Wu, C.W., Sanborn, T.J., Zuckermann, R.N., and Barron, A. E. Peptoid oligomers with alpha-chiral, aromatic side chains Effects of chain length on secondary structure. /. Am. Chem. Soc. 2001, 723, 2958-2963. 

However, similar NHC architectures employing aromatic side chains have shown more encouraging results. In 2000, Nolan and co-workers reported the synthesis and characterisation of the NHC-Ru complex 20 bearing a sterically more demanding N,N -bis-[2,6-(di-/xo-propyl)phenyl]imidazol-2-ylidene (IPr) ligand [27, 28] (Fig. 3.5). Standard RCM substrate 1 was used to test the catalytic performance of 20. The ring closure was found to be complete after 15 min by using 5 mol% 20 as catalyst at room temperature. Under identical conditions, 15... 

Compounds with conformationally restrained side chains, unsaturated side chains and aromatic side chains have been synthesised in order to better define the steric requirements of the binding site in the side-chain region. These are shown in Table 6.9. On average, the conformationally restrained... 

Absorption of proteins in the 230-300 nm range is determined by the aromatic side chains of tyrosine (Xmax = 274 am), tryptophan (Xmax = 280 nm), and phenylalanine (Xmax = 257 nm). Because the difference in the absorption spectra of native and unfolded protein molecules is generally small, difference spectra can... 

Transport of amino acids across a chloroform liquid membrane with these carriers also revealed a high specificity (Scheme 2). For efficient transport, an aromatic side chain must be present and the distance between the aryl and ammonium functions is optimal in the P-aryl systems. Neither oe-phenyl-glycine 42 nor y-phenyl-butyrine 43 are transported to significant extents 25a>. These results are shown in Table 2. The selectivity with 13 contrasts sharply for that observed with typical detergents wherein side chain hydrophobicity determines the relative transport rates. 

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