RELATIONSHIP BETWEEN BINDING AFFINITIES TO CELLULAR RETINOIC ACID BINDING-PROTEIN AND BIOLOGICAL POTENCY OF A NEW SERIES OF RETINOIDS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (1) , 190-195
Abstract
Binding affinities of a new and unusual series of retinoic acid analogs to cellular retinoic acid-binding protein, a possible mediator of their biological function in the control of differentiation and tumorigenesis, and to serum albumin, their plasma transport protein, were determined. Biological activity of these retinoids in the reversal of keratinization in hamster tracheal organ cultures was assessed and compared with their binding affinities. Analogs that possessed high biological activity showed high binding efficiency to cellular retinoic acid-binding protein. Those that were biologically less active were poor binders to the binding protein. Three retinoids, 4657-57 [4-[2-methyl-4-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E,3E-butadien-1-yl]benzoic acid], 3920-59 [5-[2-methyl-4-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E,3E-butadien-1-yl]-2-thiophenearboxylic] acid] and 4445-75 [6-[2-(2,6,6-trimethyl-1-cyclohexen-1-yl)-E-ethen-1-yl]-2-napthalenecarboxylic acid], which showed 90-100% binding efficiency of that of retinoic acid for cellular retnoic acid-binding protein expressed high biological activity detectable in the range of 10-10 M as against 10-11 M for retinoic acid. The correlation noticed in these 2 activities not only enhances the confidence in the 2 assay procedures but also paves the way for design and development of potential chemopreventive agents. No apparent differences were observed in the binding affinities of the retinoids to binding proteins of a normal tissue or a tumor tissue. No correlation existed between the binding affinities of these retinoids to serum albumin and their biological activity. Structure-activity relationships of the retinoids in relation to their binding affinities and biological activities were discussed.