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R B Cook

Publications and source records attributed to R B Cook.

26 records · Page 2Linked to original sources
PubMed1984

Binding specificity of serum amyloid P component for the pyruvate acetal of galactose.

Serum amyloid P component (SAP) is a normal plasma protein that is of interest because of its presence in amyloid deposits, its presence in normal human glomerular basement membrane, and its stable evolutionary conservation. It has calcium-dependent ligand-binding specificity for amyloid fibrils, fibronectin (Fn), C4-binding protein (C4bp), and agarose. Although the binding to agarose, a linear galactan hydrocolloid derived from some marine algae, is unlikely per se to be related to the physiological function of SAP, it does provide a model system in which to explore the precise ligand requirements of SAP. We report here that the amount of SAP from human, mouse, and plaice (Pleuronectes platessa L.) serum able to bind to agarose from different sources reflect precisely their pyruvate content. Methylation with diazomethane of the carboxyl groups in the pyruvate moiety of agarose completely abolishes SAP binding to agarose. The pyruvate in agarose exists as the 4,6-pyruvate acetal of beta-D-galactopyranose. We have therefore synthesized this galactoside, using a novel procedure, established its structure by analysis of its nuclear magnetic resonance spectra, and shown that it completely inhibits all known calcium-dependent binding reactions of SAP. The R isomer of the cyclic acetal, methyl 4,6-O-(1-carboxyethylidene)-beta-D-galactopyranoside (MO beta DG) was effective at millimolar concentration and was more potent than its noncyclic analogue, while pyruvate, D-galactose, and methyl beta-D-galactopyranoside were without effect. The autologous protein ligands of SAP presumably, therefore express a structural determinant(s) that stereochemically resembles MO beta DG. Availability of this specific, well-characterized, low molecular weight ligand for SAP should facilitate further investigation of the function of SAP and its role in physiological and pathophysiological processes.

Amyloid↗
PubMed1976

Novel analogs of tricyclic psychopharmacological agents.

The synthesis of several novel analogs of amitriptyline and chlorprothixene, in a number of which the position of the side-chain nitrogen atom rigidly fixed with respect to the tricyclic nucleus, is described. The compounds were evaluated for antidepressant-like activity in the Dopa and serotonin interaction tests and for potential antipsychotic activity in the methamphetamine interaction test. 5-(3-Dimethylaminocyclohex-1-enyl)-5H-dibenzo[a,d]cycloheptene (12) was about equipotent with imipramine in the Dopa and methamphetamine tests, and 3-chloro-10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-spiro-6'-3'-methyl-3'-azabicyclo[3.1.0]hexane (23) also displayed marked activity in the same tests. Prototype compounds for other ring systems, 3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene tropane (16) and 5-(3-dimethylaminocycloheptylidene)-10,11-dihydro-5H-dibenzo[a,d]cycloheptene (18), were less active.

Amitriptyline↗