Search PubMed⌕ Search

Biomedical subjects

R Bonnett

Publications and source records attributed to R Bonnett.

At least 37 records · Page 2Linked to original sources
PubMed1982

Concerning the structure of photobilirubin II.

Evidence is presented which supports the postulate that the photobilirubins IIA and IIB are diastereoisomers in which the C-3 vinyl group has cyclized intramolecularly. The evidence comes principally from proton n.m.r. spectroscopy at 400 MHz and from chemical considerations. The cyclic structures require the E-configuration at the C-4 double bond in the precursor; this is the first structural evidence for the Z leads to E isomerization in bilirubin and supports the view that the precursor (photobilirubin IA or IB) is (4E, 15Z)-bilirubin. Brief irradiation of photobilirubin II gives bilirubin, a new compound (photobilirubin III) and unchanged starting material. The various photoisomers are discussed in terms of their inter-relationships and biological fates.

Bilirubin↗
PubMed1982

In vivo biological activity of the components of haematoporphyrin derivative.

The in vivo biological activity of various fractions and components of haematoporphyrin derivative (HpD) have been determined by measuring the depth of necrosis of implanted tumours in mice exposed to light after the administration of standard doses of porphyrins dissolved in alkali. In this assay, haematoporphyrin, hydroxyethylvinyldeuteroporphyrin and protoporphyrin are inactive, but the mono- and di-acetates of haematoporphyrin (which are major components of HpD) and acetoxyethylvinyldeuteroporphyrin are active. However, the situation appears to be more complex than this. The normal method for preparing HpD for injection involves an alkali treatment which causes hydrolysis and elimination of the acetoxy functions, and the only recognized products (haematoporphyrin, hydroxyethylvinyldeuteroporphyrin and protoporphyrin) are inactive in the in vivo assay. It is concluded that the active component here is a porphyrin, possibly a dimer or oligomer, which is retained on the column during the normal separation by HPLC. This conclusion is supported by the observations that (i) the crude material obtained from the spent column is active without further alkali treatment, and (ii) activity develops over 30 min, when HpD or the mono- or diacetates of haematoporphyrin are treated with sodium bicarbonate in aqueous DMSO. The advantages of working with a pure substance (e.g. haematoporphyrin diacetate) rather than a mixture (HpD) are stressed.

Animals↗
PubMed1980

Mutagenicity of nitrosated alpha-amino acid derivatives N-acetyl-N'-nitrosotryptophan and its methyl ester in bacteria.

DL-N-acetyl-N'-nitrosotryptophan (I) and its methyl ester (II), readily formed under mild conditions by the reaction of nitrite with N-acetyltryptophan or its methyl ester, are model compounds for the study of the nitrosation of alpha-amino acid side chains, considered relevant to possible role of nitrosation of peptides and proteins in the aetiology of gastrointestinal cancer. Both compounds were assayed for mutagenicity in a series of Escherichia coli WP2 strains (trp- leads to trp+) and in several strains of Salmonella typhimurium (his- leads to his+), in the presence and absence of a post-mitochondrial supernatant (S9) from livers of rats treated with Aroclor 1254. Compound I was mutagenic to the following E. coli strains: WP2; WP2uvrA; WP2pKM101; WP2-98 and TA 100. Compound II was consistently less mutagenic than compound I to the E. coli strains, inactive in S. typhimurium TA 98 and TA 100, but more active than I in TA 1535. Neither compound was detectably mutagenic to E. coli WP2 lexA. Addition of S9 did not enhance the mutagenicity of either compound, and in some cases reduced the mutagenic to any of the E. coli strains tested, and nitrite alone (at pH 7.1) was very feebly mutagenic at doses where molar equivalents of compounds I were markedly active. The rate of decay of compound I in pH 5.9 was closely paralleled by decay of its mutagenicity. These data and the pattern of cytotoxicity and mutagenicity in several DNA-repair mutants of E. coli suggest that both compounds react with DNA to form excisable DNA-adducts which cause mutation by error-prone repair.

Escherichia coli↗
PubMed1979

The porphyrin pigmentation of subspecies of Bacteroides melaninogenicus.

Various subspecies of Bacteroides melaninogenicus differ in their pigmentation. Subsp. asaccharolyticus produces protohaem almost exclusively, subsp. intermedicus both protohaem and a smaller proportion of protoporphyrin, and subsp. melaninogenicus mainly protoporphyrin with a trace of protohaem. As a consequence young colonies can be differentiated by their red fluorescence in u.v. light (365nm): subsp. asaccharolyticus does not fluoresce, subsp. intermedicus shows a limited fluorescence, and subsp. melaninogenicus shows a bright fluorescence. The pigments were isolated as the dimethyl esters of protohaemin and of protoporphyrin and identified by electronic spectroscopy, mass spectrometry and comparisons by t.l.c. Incorporation of delta-aminolaevulinate into these pigments was not detected, nor was porphobilinogen formation observed. Subsp. melaninogenicus grown in the presence of [14C]protohaemin formed [14C]protoporphyrin. This appears to represent a novel biological demetallation.

Bacteroides↗
PubMed1976

Metabolism of biliverdin. Biliary excretion of bile pigments after intravenous injection of biliverdin isomers.

14C-labelled biliverdins IX alpha, beta, gamma and delta have been prepared in vitro from haemoglobin obtained from duck erythrocytes incubated with 5-amino[4-14C]-laevulinic acid. When injected intravenously into rats with biliary fistulae, about 60% of the label was recovered in the bile in 24 h after the alpha isomer was given, while approximately 10% was recovered with injection of the beta isomer. The gamma and delta isomers gave intermediate values. In each experiment, most of the recovered isotope was found in association with conjugated bile pigment. Thus, the metabolic pathway for bile pigment excretion in the rat handles the IX alpha isomer preferentially but is not specific for it.

Animals↗
PubMed1976

Neovitamin B12 (cyano-13-epicobalamin).

Beta-Epimerization in the corrinoid system has recently emerged as a complicating factor in the latter stages of the total synthesis of vitamin B12 (Eschenmoser 1971; Woodward 1973). It has also found some application in biosynthetic studies on the origin of the methyl groups in ring C (Scott, Townsend & Cushley 1973; Scott, this Discussion p. 303). This paper sets out to review briefly the beta-epimerization of corrinoid polyamides, with particular reference to our work on the neo-series which provided the first established example of this phenomenon.

Stereoisomerism↗