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Biomedical subjects

S A Barker

Publications and source records attributed to S A Barker.

At least 73 records · Page 4Linked to original sources
PubMed1982

Beta-carbolines: synthesis and neurochemical and pharmacological actions on brain benzodiazepine receptors.

We have prepared a series of tetrahydro-beta-carbolines (TH beta C), beta-carbolines (beta-C), and other nitrogen heterocycles and evaluated them in vitro with respect to their ability to bind to benzodiazepine receptors. The fully aromatic beta-C's were more potent than their corresponding TH beta C derivatives. When substituents possessing a carbonyl (CO2Me, COCH3, CHO) were introduced at the beta-C 3-position the in vitro potency was augmented. Alcohol substituents (CH2OH, CHOHCH3) demonstrated decreased in vitro potency. The importance of the carbonyl moiety was further demonstrated when beta-carboline-3-carboxylic acid was shown to bind tighter to benzodiazepine receptors at lower pH. A lower pH increases the concentration of the acid and decreases the concentration of the anion. 3-(Hydroxymethyl)-beta-carboline (24), 3-formyl-beta-carboline (25) and 3-acetyl-beta-carboline (27) were benzodiazepine antagonists in vivo. Methyl isoquinoline-3-carboxylate (31a) also had in vitro activity. The same structure-activity relationships seen in beta-C's were also observed for isoquinolines.

Animals↗
PubMed1980

Hyperformaldehydism: a unifying hypothesis for the major biochemical theories of schizophrenia.

A biochemical hypothesis concerning the etiology of schizophrenia is presented. This hypothesis postulates the presence of a genetically determined lesion in the disposition of one-carbon units leading to elevated levels of formaldehyde, i.e hyperformaldehydism. The relationships between this hypothesis and the existing major biochemical hypotheses of schizophrenia regarding dopamine and transmethylation are discussed.

Carbolines↗
PubMed1977

Active water-insoluble derivatives of papain and other enzymes based on preformed diazonium-type supports.

Papain (EC 3.4.22.2) has been coupled to supports of titanium (IV) oxide and cellulose, which are particulate and pre-coated with diazotised 1,3-diaminobenzene, giving water-insoluble and stable derivatives which possess low proteolytic activity but high esterolytic activity. In addition the reversible binding of zinc (II) at the active site of papain has been exploited to inhibit protectively the enzyme during its linkage to the aforementioned supports, thereby yielding water-insoluble derivatives of papain having superior activity upon reactivation with EDTA. Application of the improved procedure of enzyme coupling to macroporous cellulose particles gave a water-insoluble derivative of papain having further enhanced proteolytic activity. Other properties of the water-insoluble derivatives of papain and of similarly prepared water-insoluble conjugates of urease (EC 3.5.1.5) and cholinesterase (EC 3.1.1.8) with cellulose are also reported.

Cellulose↗
PubMed1974

The reaction of an alpha-aza-amino acid derivative with chymotrypsin and its use as a ligand for covalent affinity purification.

1. Chymotrypsin is inactivated by N-acetyl-alpha-azaphenylalanine phenyl ester (phenyl N(2)-acetyl-N(1)-benzylcarbazate) in a stoicheiometric reaction. 2. The inactivation is reversible spontaneously (first-order rate constant is 1.2x10(-4)s(-1)) and accelerated by the presence of hydroxylamine. 3. Polymers based on polyacrylamide and carrying ligands containing the alpha-azaphenylalanine phenyl ester group were prepared. 4. Chymotrypsin reacts with these polymers and is removed by them from solution. Trypsin reacts less rapidly. 5. Chymotrypsin is slowly released from the polymer spontaneously and more rapidly on treatment with hydroxylamine. 6. The reaction of trypsin can be inhibited by competitive inhibitors. 7. Chymotrypsin was separated from trypsin by the selective bonding of chymotrypsin on to and its subsequent liberation from one of the polymers described.

Acrylamides↗
PubMed1974

Active insolubilized antibiotics based on cellulose-metal chelates.

Cellulose was converted into a more reactive form by chelation with the transition metals titanium(III), iron(III), tin(IV), vanadium(III), and zirconium(IV). The remaining unsubstituted ligands of the transition metal ions were found to be amenable to replacement by electron-donating groups of antibiotic molecules. Ampicillin, gentamicin, kanamycin, neomycin, paromomycin, polymyxin B, and streptomycin were used as antibacterial antibiotics, and amphotericin B and natamycin were used as antifungal antibiotics. Antibacterial activity of the products was tested against two gram-positive and two gram-negative bacteria, and antifungal activity was tested against four fungi. That the antibacterial antibiotics had complexed with the cellulose-metal chelates was demonstrated in that the product cellulose-metal-antibiotic chelates exhibited antibiotic activities whereas the metal chelates of cellulose themselves were inactive. Of 140 tests conducted, cellulose-metal-antibiotic chelates were active in 102 cases. Since the antibiotic derivatives were water insoluble and in fact retain some of the antibacterial activities of the parent compounds, the chelation method provides a facile way of rendering cellulose surfaces, etc., resistant to microbial attack over and above that degree of protection afforded by noncovalent adsorption of the antibiotic to cellulose itself. The underlying principles of the chelation reactions involved are discussed in detail.

Anti-Bacterial Agents↗