Phenylalanine, protonated

Morris and Hall (35) have examined a series of carbohydrates. Larger molecules are, of course, feasible. Chan and Markley (36) have assigned histidine, tyrosine and phenylalanine protonated carbon resonances in uniformly enriched (20%) oxidized ferro-dixin by heteronuclear H/C 2D shift correlation NMR. Polypeptide resonances have also been assigned using C/H 2D NMR (3J7,3f3). In these systems H/H homonu-clear, H/C heteronuclear and N/H heteronuclear 2D techniques have allowed direct confirmation of assignments and connectivities, in particular the NH nitrogens and protons. 

THE MECHANISM The mechanism shown outlines the major stages in carboxypeptidase-catalyzed hydrolysis of a peptide in which the C-terminal amino acid is phenylalanine. Proton transfers accompany stages 2 and 3 but are not shown. Only the major interactions of the substrate with the carboxypeptidase side chains are shown although others may also be involved. 

A related approach at a molecular level has been used, with methyl- Cs-MNP to examine the proximity of the spin-adduct methyl groups to aromatic tyrosine and phenylalanine protons in equine myoglobin. By use of this approach it has been shown that radical generation and hence spin-adduct formation occurs solely at the Tyr-103 residue. ... 

A system exhibiting chiral recognition. The chiral macrotricyclic tet-raamide (250) (Lehn, Simon Moradpour, 1978) has been used for the complexation, extraction and transport of primary ammonium salts. The tetraamide was used rather than the corresponding tetraamine because of the lower basicity of the nitrogens in the former ligand. This avoids the possibility of proton transfer occurring from the primary ammonium substrates R-NH3+ used as guests. In a typical experiment, a solution of a primary ammonium salt, such as naphthylethyl ammonium or phenylalanine methylester hydrochloride in hydrochloric acid was... 

The HOPG (highly oriented pyrolytic graphite) carbon electrode chemically modified with (5[-phenylalanine at the basal surface led to 2% ee in the reduction of 4-acetylpyridine [377]. A cathode modified with a chiral poly(pyrrole) reduced 4-methylbenzophenone or acetophenone in DMF/LiBr and phenol as proton donor to 1-phenylethanol with up to 17% ee [382]. Alkyl aryl ketones have been reduced to the corresponding alcohols at a Hg cathode in DMF/water in the presence of (1R,2S)-A,A-dimethylephedrinium tetrafluorobo-rate (DET), producing (5 )-l-phenylethanol with 55% ee from acetophenone. Cyclovoltammetry supports an enantioselective protonation of the intermediate (PhCOH(CH3)) [383]. 

This enzyme [EC 5.1.1.11], also known as phenylalanine racemase (ATP-hydrolyzing), catalyzes the reaction of ATP with L-phenylalanine to produce o-phenylalanine, AMP, and pyrophosphate. In this unusual racemase reaction, a thiol group of an enzyme-bound pantotheine forms a thiolester from an initial aminoacyl-AMP intermediate then, as is typical of acyl thioesters, the a-proton becomes labile, thereby permitting reversible inversion of configuration to produce an equilibrated mixture of thiolester-bound enantiomers. Hydrolysis of the thiolester yields the product. 

Based on the known substrate specificity of a-chymotrypsin, phenylalanine has been chosen as the amino acid at the Pi position (P-nomenclature according to Schechter and Berger) [55]. The a-proton at Pi has been substituted either by methyl or trifluoromethyl. Substitutions beyond Pi contain trifluoromethyl alanine or aminoisobutyric acid. Therefore, each fluorosubstitution can be compared to its natural as well as fluorine-free a-substituted analog, thereby enabling differentiation of the steric and electronic effects. Scheme 2 summarizes the amino acids that have been used in this study. 

PAL is one of the best-characterized enzymes of plant secondary metabolism. It converts l-phenylalanine into tran -cinnamate ( -cinnamate) by the tra 5-elimination of ammonia and the pro-StS proton (see Ref. 4 for a full reaction discussion). The enzyme, which requires no cofactor, is a tetramer of 310-340 kDa. A cDNA for PAL was first isolated from Petrose-linum crispum (parsley), and others have subsequently been isolated from numerous species. Often PAL is produced from a multigene family and is present in a variety of isoenzyme forms. 

A similar situation is found in the structure of putrescine diphosphate " (a model system for amine-nucleic acid interactions) which divides into layers of HjPOJ anions bridged by protonated putrescine (1,4-diamino-n-butane) cations. In a real biological system (yeast phenylalanine transfer RNA) phosphate residues are found to be enveloped by the polyamine spermine [NH2(CH2)jNH(CH2)4NH(CH2)jNH2] which again adopts a linear, nonchelating conformation. ... 

A consequence of the existence of this equilibrium was the formation of a monosulfide (114) in the reaction of the simple dehydrocyclodipeptide (113) with an alanine or phenylalanine residue, as shown in Scheme 36. The reaction could have proceeded by replacement of the OMe by SH, followed by protonation of the exocyclic double bond and intramolecular attack by the thiol group. Alternatively, the m-dithiol could have been in equilibrium with the /rani-dithiol in the latter, a traw.v-annular attack could have generated the monosulfide. 

On the basis of the above data, a tentative hypothesis has been advanced for the observed asymmetric induction. The carbonyl oxygen of benzaldehyde forms a H-bond with the piperazine ring NH of the histidine, the imidazole is protonated by the HCN, and the resulting cyanide ion attacks the si face of the activated carbonyl group since the re face is blocked by the phenyl ring of the phenylalanine, as seen in the Fig. 1. 

Fig. 5. 500 MHz HRMAS H NMR spectra of FMOC-isoleucine on Wang resin swollen in DMF- 7 and spun at 4 kHz. Spectrum A shows the presence of dissolved phenylalanine peaks, particularly around 3.0 ppm from its methylene protons, and residual protons of the solvent. Application of a diffusion filter using gradients selectively removes these signals in spectrum B. Reproduced with permission from Ref. 50. Copyright 1999 Elsevier.

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