II. CHEMISTRY 567 



activity not only in relation to biotin but also to oxybiotin and desthio- 

 biotin. In replacing biotin with oxybiotin or desthiobiotin, amounts of the 

 compounds biologically equivalent to the indicated amounts of biotin are 

 used for determining the molar inhibition ratios. The available data are 

 summarized in Table IV. 



It is of interest that the inhibitory effect of desthiobiotin appears to V)e 

 due only to the dextrorotatory form which is also the only form which 

 exerts a growth-promoting activity for Saccharomyces cerevisiae. Oxybiotin 

 may overcome the toxicity of desthiobiotin for Lactobacillus casei, but it is 

 considerably less effective than biotin. The results indicate that in the 

 competition for the enzyme involved the affinity of oxybiotin is much 

 lower than that of biotin. 



Some of the inhibitory analogs tested represent modifications of desthio- 

 biotin in which the length of the side chain containing the carboxyl group 

 is varied, the 5-methyl group is omitted, or the carboxyl group is replaced 

 by a sulfonic acid group (Table IV). Among these analogs, dl-2-oxoA- 

 imidazolidinecaproic acid proved to be especially potent in preventing the 

 utilization of desthiobiotin for Escherichia coli. Since in this case biotin 

 prevents the inhibition non-competitively, the analog appears to prevent 

 the con\-ersion of desthiobiotin to biotin. In other instances, the utilization 

 of both compounds, biotin and desthiobiotin, may be inhibited. 



The claim that desthiobiotin may have an inhibitory effect on the growth 

 of tumors'" has not yet been confirmed. 



e. Homologs and Sulfone Analogs of Biotin 



The most potent inhibitors are biotin sulfone, d^homobiotin, and their 

 various analogs (Table V). (In homobiotin the side chain contains 5; in 

 norbiotin, 3 (CH2).) 



/. A nalogs of Oxybiotin 



The homologs of oxybiotin and related compounds are practically inac- 

 tive as inhibitors for biotin but show marked activity in preventing the 

 utilization of oxybiotin (Table VI). 



The fermentation ratio of biotin-deficient yeast cells is stimulated in 

 the presence of ammonium sulfate by biotin or oxybiotin. rf/-Homooxy- 

 biotin or the sulfonic acid analog of oxybiotin will prevent the fermentation 



168 K. Dittmer and V. du Vigneaud, J. Biol. Chem. 169, 63 (1947). 



'"R. Duschinsky and L. A. Dolan, J. Am. Chem. Sac. 68, 2350 (1946). 



"0 L. L. Rogers and W. Shive, J. Biol. Chem. 169, 57 (1947). 



1" II. McKennis, Jr., and V. du Vigneaud, /. Am. Chem. Soc. 68, 832 (1946). 



'" R. Duschinsky and S. H. Rubin, J. Am. Chem. Soc. 70, 2546 (1948). 



'^^ J. C. Keresztesy, D. Laszlo, and C. Leuchtenberger, Cancer Research 6, 128 (1946), 



