Pyrrole amino acid

Baird, E.E. and P.B. Dervan. Solid phase synthesis of polyamides containing imidazole and pyrrole amino acids./. 

The bone collagen cross-link (+)-deoxypyrrololine has potential clinical utility in the diagnosis of osteoporosis and other metabolic bone diseases. Intrigued by its novel structure and its promise to allow the early discovery of various bone diseases, the research team of M. Adamczyk developed a convergent total synthesis for this 1,3,4-trisubstituted pyrrole amino acid. The key step of the synthesis was the union of the nitroalkane and aldehyde fragments to obtain a diastereomeric mixture of the expected -nitro alcohol in good yield. This new functionality served as a handle to install the pyrrole ring. 

A modified 1,4 diketone 17 was employed for the microwave-assisted preparation of amino acids containing the pyrrole ring (Scheme 6). The products were further employed for the introduction of this original moiety into a peptide sequence [33]. 

Another series of pyrroles, structurally related to amino acids, was obtained in a microwave-assisted solvent-free condensation of a-amino acid methyl esters with chloroenones, which provided the four-carbon unit of the pyrrole. The reaction was carried out by mixing the reagents on silica gel and irradiating for 2-6 min inside a multimode microwave cavity (Scheme 7). The authors reported higher yields and cleaner products when microwaves were used instead of conventional heating [34],... 

Fig. 3.15 Model for allosteric inhibition of a protein-DNA complex by a polyamide-inter-calator conjugate. (Top) The GCN4 homodimer (yellow) is displaced by the intercalating moiety (green) of the polyamide conjugate. Blue and red spheres represent pyrrole and imidazole amino acids, respectively. The blue diamond represents / -alanine. (Bottom, left) Hydrogen-bonding model of an eight-ring hairpin polyamide-intercalator conjugate...

WvRTZ, N.R., J.M. Turner, E.E. Baird, and P. B. Dervan. Fmoc solid phase synthesis of polyamides containing pyrrole and imidazole amino acids. Org. Lett. 2001, 3, 1201-1203. 

In the aligned primary structures of class I decarboxylases, the conserved amino acid residues are scattered over their primary structures. There have been few reports to identify the amino acid residues essential for catalytic activity or substrate binding. Huang et al. reported the E-X-P motif in the alignment analysis for 4-hydroxybenzoate decarboxylase of C. hydroxybenzoicum and its homologous unidentified proteins. The E-X-P motif is also conserved in pyrrole-2-carboxylate decarboxylase and indole-3-carboxylate decarboxylase (unpublished data). However, the corresponding motif sequence is not observed in the primary structures of 3,4-dihydroxybenzoate decarboxylase of E. cloacae P241. ... 

The analytical data obtained, particularly by the PUMA mass spectrometer on board Vega 1 during the flyby, indicate the presence of a large number of linear and cyclic carbon compounds, such as olefins, alkynes, imines, nitriles, aldehydes and carboxylic acids, but also heterocyclic compounds (pyridines, pyrroles, purines and pyrimidines) and some benzene derivatives no amino acids, alcohols or saturated hydrocarbons are, however, present (Kissel and Krueger, 1987 Krueger and Kissel, 1987). 

Reaction of the thia-amino acid 392 with trifluoroacetic anhydride gave the 2,2,2-trifluoro-l-[7-(trifluoromethyl)-l//-pyrrolo[l,2-c]-[l,3]thiazol-6-yl] ethanone pyrrole 395. The formation of the pyrrole can be rationalized by a sequence involving trifluoroacetylation of the enamine 392 affording dione 393 followed by loss of water and carbon dioxide to give the aromatic product 395. These decarboxylations afford fluorinated derivatives of heterocyclic skeletons known to exhibit interesting biological activity (Scheme 58) <2000T7267>. 

Krausz el al. have synthesised two series of amino acid porphyrinylsugar derivatives (Fig. 5). One of them involves the coupling of adequate glycoporphyrin derivatives, prepared by pyrrole/aldehyde condensation methodology, with 9-fluorenylmethoxycarbonyl-L-alanine (Fmoc-L-alanine) to give the tri-, di-, and mono-alanine glycoporphyrin derivatives 54—57 after the deprotection step the other series (58) involves a glucosylamino acid moiety instead of the alanine in their preparation.21,44... 

Antibodies also well catalyze the reactions where a molecule should he forced to adopt a particular and reactive conformation, thanks to privileged interactions with the amino acids of the binding site. For example, ahzymes with a ferrochelatase activity, 7G12, force the mesoporphyrin IX ring to adopt a distorted conformation favorable to the insertion of a Cu ion in the center of the macrocycle,thanks to an interaction with the HlOOc methionine which constrains one of the pyrrole rings to be left outside the plane of porphyrin (Figure 24). 

As with any metalloprotein, the chemical and physical properties of the metal ion in cytochromes are determined by the both the primary and secondary coordination spheres (58-60). The primary coordination sphere has two components, the heme macrocycle and the axial ligands, which directly affect the bound metal ion. The pyrrole nitrogen donors of the heme macrocycle that are influenced by the substitutents on the heme periphery establish the base heme properties. These properties are directly modulated by the number and type of axial ligands derived from the protein amino acids. Typical heme proteins utilize histidine, methionine, tyrosinate, and cysteinate ligands to affect five or six coordination at the metal center. 

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