B10T1N 555 



cated otherwise, are listed in terms of the molar inhibition ratio, 48 which 

 has been defined as the number of molecules of the inhibitor necessary 

 to prevent the biological effect of one molecule of biotin. The molar in- 

 hibition ratio 4S of inhibitor to biotin is obtained experimentally by 

 determining the amount of the inhibitor required to reduce the growth 

 obtained with 0.0002 y of biotin to the level of growth obtained with 

 0.0001 y of biotin. The molar inhibition ratio is approximately twice the 

 inhibition index for half-maximum inhibition of growth, and is usually 

 considerably less than the inhibition index just necessary for complete 

 inhibition of growth. In replacing biotin with oxybiotin (O-heterobiotin) 

 or desthiobiotin, amounts of the compounds biologically equivalent to 

 the indicated amounts of biotin are used for determining the molar 

 inhibition ratios. 



Since ( + ) desthiobiotin is approximately twice as active as dl- 

 desthiobiotin in preventing the utilization of biotin by Lactobacillus 

 casei, the inhibitory action appears to be the result of the action of only 

 the dextrorotatory form, which is also the only form which appears to 

 exert a growth-promoting activity for Saccharomyces cerevisiae. The 

 oxygen analogue of biotin is also capable of preventing the toxicity of 

 desthiobiotin for Lactobacillus casei, but is much less effective. The 

 results indicate that the affinity of oxybiotin for the enzyme involved is 

 considerably less than that of biotin. 



The more effective inhibitory analogues of desthiobiotin, which are 

 indicated by the following formulas, represent modifications of desthio- 

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

 CO CO 



/ \ / \ 



HN NH HN NH 



HC CH H 2 C CH 



CH, CH 2 — (CH 2 ) 7 — COOH CH 2 — (CH 2 ) 4 — COOH 



VL-5-methyl-2-oxo-4~ mj-2-oxo-It-imidazolidine- 



imidazolidinepelargonic acid caproic acid 



CO 

 / \ 



HN NH 



HC CH 



CH 3 



CH 2 -(CH 2 ) 4 — S0 3 H 



T>ii-5-methyl-2-oxo-Jr-iinidazolidine- 

 pentanesidfonic acid 



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

 by a sulfonic acid group. These compounds have not as yet been reported 

 to be particularly effective antagonists of biotin. 



