558 BIOTIN 



j^y"io6, 107 jg expressed as the ratio of the concentration of analog to biotin 

 at which one-half of the biotin remains free and available for growth of the 

 test organism. Thus, the ratio will be low for analogs for which avidin has 

 considerable affinity and high for those analogs that do not combine readily 

 with avidin. With this technique, synthetic ( — )-biotin and dZ-allobiotin 

 have shown no significant affinity for avidin. The affinity ratios for biocy- 

 tin,^"* d^epiallobiotin, d/-desthiobiotin, and 5-(2,3-ureylenecyclohexyl) va- 

 leric acid were 3, 6, 10, and 14, respectively. 7-(3 ,4-Ureylenecyclohexyl)bu- 

 tyric acid and 5-(3,4-ureylenecyc]ohexyl)valeric acid have shown definite 

 but very low affinity for avidin. 



Among other analogs the following have been found to combine with 

 avidin: rf/-oxybiotin, c?Z-oxybiotin methyl ester, d^hexahydro-2-oxo-lH- 

 furo[3,4]imidazole-4-pentanol,^''^ and 2-oxo-4-imidazofidine valeric, caproic, 

 enanthic, and caprylic acids. ^°^ 



The inability of m-3,4-diamino-2-tetrahydrothiophenevaleric acid (the 

 diaminocarboxylic acid corresponding to biotin), f , Tj-diaminopelargonic 

 acid (an analog of desthiobiotin), and (i/-cis-3,4-diamino-2-tetrahydrofur- 

 aurvaleric acid (corresponding to oxybiotin) to combine with avidin^"* '^^^ 

 appears to confirm the assumption that avidin combinability is a function 

 of the imidazolidine ring. Since desthiobiotin and other similar sulfur-free 

 derivatives as well as the methyl ester of oxybiotin or the alcohol analog of 

 oxybiotin combine with avidin, neither the sulfur atom nor the carboxyl 

 group of the biotin molecule is essential for the bonding with avidin. ^"^^ ^°^ 



Some of the biotin is excreted in the urine of normal rats and in human 

 urine as avidin-uncombinable fractions."^- "- The chemical nature of the 

 biotin derivatives in the urine, termed miotin, tiotin, and rhiotin,^^^ which — 

 it is claimed — differ from each other by their resistance to heat, avidin 

 combinability, and varying activity for yeast and Rhizobium, has not yet 

 been determined. 



G. SPECIFICITY 

 1. Biotin 



The configuration of the biotin molecule and of its derivatives deter- 

 mines the specificity of their action for animals and microorganisms. 



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 "13 D. Burk and R. J. Winzler, Science 97, 57 (1943). 



