FL'TURE PROBLEMS IN MOLECULAR INTERACTIONS 317 



By group-specific reactants it has been demonstrated that certain protein 

 side-chains may be necessary for the binding. The binding of testosterone 

 to serum albumin is especially interesting in this connection because the 

 substance is neutral and changes in total protein charge would not be 

 expected to be of much importance. The binding energy is approximately 

 — 6 kcal/mole and the maximal number of testosterone molecules bound is 

 5 or 6 per molecule of protein (Levedahl and Perlmutter, 1956). Two tyrosine 

 groups in the serum albumin seem to be involved in the binding of one 

 testosterone molecule since the effect of pH on binding indicates that the 

 testosterone is released when the phenolic groups become ionized. Although 

 iodination of the tyrosine rings does not alter binding significantly, keten- 

 ization of the phenolic groups prevents binding (Oyakawa and Levedahl, 

 1958). It was postulated that the testosterone molecule lies parallel to 

 the tyrosine rings and that the hydroxyl or ketone groups on the sterol 

 react with the phenolic groups. In this instance the specificity of binding 

 seems to be rather high and might be extended to other sterols, such as 

 cortisone and estradiol (Eik-nes et al., 1954). A very interesting discussion 

 of structural specificity in sterol binding has been given by Turner (1954). 

 When enzyme inhibitors are optically active, it is generally found that 

 differences in potency are observed between the isomers, so that the demon- 

 stration by Karush (1952) that optically isomeric dyes are bound different- 

 ly to serum albumin is important in iUustrating such specificity. The rel- 

 ative positions of the phenyl ring in 



(CH3),X— cp— X=X— cp— COXH— C^COO" 



<P 



must be important in the affinity of this dye for the protein, indicating 

 a specific configuration at the landing sites. 



Finally, the concept of specific binding is strengthened by the fact 

 that for a particular compound, binding may occur to only certain proteins 

 and not to others, even though the over-all net charge on the proteins may 

 be the same. Thus with methyl orange, only serum albumin and /?-lacto- 

 globulin of the some dozen proteins studied were found to present adequate 

 binding sites (Klotz and Urquhart. 1949 b). Proteins with similar physical 

 and chemical characteristics often exhibit preferential binding for small 

 molecules and ions, indicating that certain group configurations on the 

 protein surface are necessary. 



FUTURE PROBLEMS IN MOLECULAR INTERACTIONS 



A cycloramic approach to the subject of molecular forces in enzyme inhi- 

 bition has been presented and it is to be regretted that in most cases the 

 real objects in the picture are slight in comparison with the painted back- 



