Symmetrical features in polypeptide hormone-receptor interactions.

Symmetrical features were observed in the amino acid sequences of some biologically active peptides. It is suggested that this approximate symmetry is reflected in the conformations of the peptides at their respective biological receptors, and has arisen by natural selection as both peptides and receptors evolved to optimise their mutual fit. It follows that the binding site for each peptide at its receptor would share the same symmetry element. This would arise if the peptide binds to two symmetrically related similar or identical submits in the receptor.

Physicochemical-activity relationships in asymmetrical analogues of methoxychlor.

Compounds of the general formula 2-aryl-2-(p-methoxyphenyl)-1,1,1-trichloroethane have been prepared and tested for toxicity toward houseflies, pretreated for 1 h with 2mug of piperonyl butoxide. The majority of the compounds synthesized were chosen with the aid of computer programs designed to ensurewell-spread sets of minimally correlated physicochemical parameter values. A nonlinear two-dimensional representation was used to map the active region of physiochemical parameter space and a regression equation was obtained relating the observed toxicity to a combination of these physicochemical parameters. The equation indicates that toxicity increases with the hydrophobicity of the molecules but is decreased markedly by the introduction of bulky substituents into the ortho positions of the benzene ring and less markedly by bulky substituents in the meta and para positions. Substituents which donate electrons to the benzene ring by the "resonance" effect favor high toxicity. The equation performs well in forecasting the toxicity of further members of the series.

Physicochemical-activity relationship in practice. 2. Rational selection of benzenoid substituents.

A rational method is presented for the selection of substituents to be introduced into a benzenoid ring system of a biologically active compound in order to a defined physicochemical parameter space. The method, which may be readily programmed for use on a computer, relies on maintaining a minimum distance between compounds in the multidimensional physicochemical parameter space. The series of compounds produced will then have a well-spread set of minimally correlated physicochemical parameter values and could thus be used for the reliable correlation of the variation in the biological activities of the members of the series with changes in these physicochemical parameters. Some examples of the use of the present method under various conditions are given, and it is compared with alternatives in the literature.

The selection of arylamidinourea antimalarials by their predicted physicochemical properties.

1 A small group of arylamidinoureas for which the predicted physicochemical properties were widely spaced and uncorrelated was selected for study.2 The antimalarial activity of each compound was measured against three species of plasmodium. Three corresponding regression equations were calculated relating the potency of each compound to its predicted physicochemical properties.3 The potency of further test compounds was forecast for each species, by using the corresponding regression equation. These forecasts were compared with the measured activity of the test compounds, and were better than would be expected by chance.4 It is suggested that only a few compounds in a series need be studied initially in order to derive regression equations with worthwhile predictive properties, if the compounds are selected according to appropriate criteria.