Total synthesis of symmetric bile pigments: Mesobilirubin‐IVα, mesobilirubin‐XIIIα and etiobilirubin‐IVγ

Trull, Francesc R.; Franklin, R. W.; Lightner, David A.

doi:10.1002/jhet.5570240614

Cited by 68 publications

(19 citation statements)

References 17 publications

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“…Biliverdin Reductase Assays-The biliverdin isomers used in this study were synthesized from mono-and dipyrrole components as described previously (27)(28)(29)(30)(31)(32)(33)(34). Dried preparations were dissolved in Me 2 SO to give a final stock concentration of 1 mM.…”

Section: Enzyme Assaysmentioning

confidence: 99%

Studies on the Specificity of the Tetrapyrrole Substrate for Human Biliverdin-IXα Reductase and Biliverdin-IXβ Reductase

Cunningham

Dunne

Sabido

et al. 2000

Journal of Biological Chemistry

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A comparison of the initial rate kinetics for human biliverdin-IX␣ reductase and biliverdin-IX␤ reductase with a series of synthetic biliverdins with propionate side chains "moving" from a bridging position across the central methene bridge (␣ isomers) to a "␥-configuration" reveals characteristic behavior that allows us to propose distinct models for the two active sites. For human biliverdin-IX␣ reductase, as previously discussed for the rat and ox enzymes, it appears that at least one "bridging propionate" is necessary for optimal binding and catalytic activity, whereas two are preferred. All other configurations studied were substrates for human biliverdin-IX␣ reductase, albeit poor ones. In the case of mesobiliverdin-XIII␣, extending the propionate side chains to hexanoate resulted in a significant loss of activity, whereas the butyrate derivative retained high activity. For human biliverdin-IX␣ reductase, we suggest that a pair of positively charged side chains play a key role in optimally binding the IX␣ isomers. In the case of human biliverdin-IX␤ reductase, the enzyme cannot tolerate even one propionate in the bridging position, suggesting that two negatively charged residues on the enzyme surface may preclude productive binding in this case. The flavin reductase activity of biliverdin-IX␤ reductase is potently inhibited by mesobiliverdin-XIII␣ and protohemin, which is consistent with the hypothesis that the tetrapyrrole and flavin substrate bind at a common site.

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Section: Enzyme Assaysmentioning

confidence: 99%

Studies on the Specificity of the Tetrapyrrole Substrate for Human Biliverdin-IXα Reductase and Biliverdin-IXβ Reductase

Cunningham

Dunne

Sabido

et al. 2000

Journal of Biological Chemistry

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“…The dipyrrinone coupling partner with the threeethyls (3) was designed to have improved solubility in nonpolar organic solvents. It was synthesized by condensing ethyl 5-formyl-3,4-diethylpyrrole-2-carboxylate (6) with 3-ethyl-4-methylpyrrolinone (5). The former was prepared in good yield by ceric ammonium nitrate oxidation of the known pyrrole ester 8 [19±21], the latter in excellent yield from -tosylpyrrole 10, which was synthesized by reaction of p-toluenesulfonylmethyl isocyanide (TosMIC) with 3-nitropentan-2-ol acetate according to the Barton-Zard method [22].…”

Section: Synthetic Aspectsmentioning

confidence: 99%

An Intramolecularly Hydrogen Bonded Dihydrotripyrrinone

Tipton

Lightner

1999

Monatshefte fuer Chemie

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A yellow tripyrrole analog (1) of bilirubin has been synthesized, and its lone propionic acid group is found to engage in conformation determining, intramolecular hydrogen bonding in solution and in the crystal. Molecular modelling and X-ray crystallography reveal an abbreviated ridge-tile or L-shape conformation in which an essentially planar dipyrrinone is hydrogen bonded to the single opposing propionic acid group. In the (arbitrary) (P)-helicity ridge-tile, the torsion angles about C(10) are computed to be 55 and 61 by molecular dynamics and found to be 66 and 53 in the crystal. Such torsion angles lead to an interplanar dihedral angle ($93 ) between the dipyrrinone and its adjoining pyrrole that is very close to the dihedral angle ($98 ) found in intramolecularly hydrogen bonded bilirubin.

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“…Bilirubin III (BR-III, 4) and bilirubin XIII (BR-XIII, 5) were isolated by preparative high pressure liquid chromatography (HPLC) [32] of a puri®ed mixture of bilirubins III, IX and XIII produced by acid catalyzed scrambling of bilirubin [33]. Xanthobilirubic acid (XBR, 7) and mesobilirubin XIII (MBR-XIII, 6) were prepared by total synthesis [34,35]. All pigments were >94% homogeneous by HPLC.…”

Section: Chemicalsmentioning

confidence: 99%

Induction of Wavelength-Dependent Photochemistry in Bilirubins by Serum Albumin

McDonagh

Agati

Lightner

1998

Monatshefte fuer Chemie

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Quantum yields for Z > E photoisomerization of the natural bi-chromophore bilirubin IX in ammoniacal methanol solution were found to vary with excitation wavelength, whereas no variation (within experimental error) was observed for xanthobilirubic acid and for symmetrically substituted bilirubins (bilirubin III, bilirubin XIII, and mesobilirubin XIII) in the same solvent. The quantum yield for Z > E photoisomerization of xanthobilirubic acid bound to human serum albumin was also invariant with excitation wavelength. In contrast, quantum yields for Z > E photoisomerization of the symmetrically-substituted bilirubins did show marked excitation wavelength dependency when they were bound to human serum albumin. These results show that quantum yields for Z > E photoisomerization of bilirubins are markedly sensitive to protein binding and to the nature of pyrrole ring -substituents. They also demonstrate that wavelength-dependent photochemistry is characteristic of bilirubins with non-identical pyrromethenone chromophores, as expected from exciton coupling theory, and that complexation with albumin induces wavelengthdependent photochemistry in symmetrically substituted bilirubins.

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Total synthesis of symmetric bile pigments: Mesobilirubin‐IVα, mesobilirubin‐XIIIα and etiobilirubin‐IVγ

Abstract: The unnatural bile pigments mesobilirubin‐IVα, mesobilirubin‐XIIIα and etiobilirubin‐IVγ were synthesized following self‐coupling of the pyrromethenones ψ‐xanthobilirubic acid methyl ester, xanthobilirubic acid methyl ester and kryptopyrromethenone, respectively.

Cited by 68 publications

References 17 publications

Studies on the Specificity of the Tetrapyrrole Substrate for Human Biliverdin-IXα Reductase and Biliverdin-IXβ Reductase

Studies on the Specificity of the Tetrapyrrole Substrate for Human Biliverdin-IXα Reductase and Biliverdin-IXβ Reductase

An Intramolecularly Hydrogen Bonded Dihydrotripyrrinone

Induction of Wavelength-Dependent Photochemistry in Bilirubins by Serum Albumin

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