DISPLACEMENT OF THYROXINE FROM HUMAN THYROXINE-BINDING GLOBULIN BY ANALOGUES OF HYDANTOIN. STERIC ASPECTS OF THE THYROXINE-BINDING SITE*

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Abstract
5,5 Diphenylhydantoin (DPH) displaces I-131 thyroxine (T4) from its serum alpha globulin carrier. This effect can be reversed by dialyzing plasma containing DPH against saline for 48 hours. Furthermore, the same alpha globulin binding capacity is attained by the addition of progressive increments of stable T4, both in the presence and in the absence of DPH. These findings indicate a competitive binding of DPH and T4 at the alpha globulin site. Of 13 analogues of hydantoin tested that failed to displace T4-I-131 from alpha globulin, none had a diphenyl substituent at 5-C of the hydantoin ring. Of 10 hydantoin analogues capable of displacing T4-1-131 from alpha globulin. all but one possessed a diphenyl group at 5-C. The exception had one phenyl and one cyclohexene grouping at 5-C. On the basis of the findings above and known interatomic distances and angles we postulate that an analogy between DPH and T4 exists by virtue of the diphenyl linkage of DPH at 5-C and the diphenyl ether linkage of T4, and suggest that both substances bind at a sterically complementarv area on the receptor site.