BIOTIN 561 



affinity" for avidin is determined by varying the analogue concentration 

 when biotin and avidin are present in stoichiometric amounts. The "rela- 

 tive affinity" is expressed as a ratio of concentration of analogue to biotin 

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

 a test organism. With this technique, ( — ) biotin and DL-allobiotin were 

 found to have no significant affinity for avidin, but DL-epi-allobiotin has 

 an affinity ratio of approximately 6. The affinity ratios for DL-desthiobio- 

 tin and 8- (2,3-ureylenecyclohexyl) valeric acid are 10 and 14, respectively. 

 y-(3,4-Ureylenecyclohexyl) butyric acid and 8-(3,4-ureylenecyclohexyl)- 

 valeric acid have a definite ability to combine with avidin, but the ratios 

 are too high to be determined. 



Other than those mentioned above, the following have been found to 

 combine with avidin: DL-oxy biotin, 34 DL-oxybiotin methyl ester, 34 dl- 

 hexahydro-2-oxo-lH-furo[3,4]imidazole-4-pentanol 34 and 2-oxo-4-imid- 

 azolidinevaleric, caproic, enanthic and caprylic acids. 48 



The inability of «s-3,4-diamino-2-tetrahydrothiophenevaleric acid 

 (the diaminocarboxylic acid corresponding to biotin) to combine with 

 avidin was the basis for the first suggestion that avidin combinability 

 was a function of the imidazolidone ring. 48> 49 This is further substantiated 

 by the inability of £,??-diaminopelargonic acid, 48 an analogous derivative 

 of desthiobiotin, and DL-c{s-3,4-diamino-2-tetrahydrofuranvaleric acid, 34 

 corresponding to oxybiotin, to combine with avidin. 



Since desthiobiotin 48 and other derivatives not containing the sulfur 

 atom combine with avidin, the sulfur atom does not appear essential for 

 the bonding. Also, the methyl ester of oxybiotin 34 and the alcohol 

 analogue of oxybiotin 34 in which the carbinol group replaces the carboxyl 

 group combine with avidin, indicating that the carboxyl group is not 

 essential for this activity. However, there appears to be structural 

 specificity with regard to the configuration of the molecule necessary for 

 avidin combinability. 



Bibliography 



1. Wildiers, E., Cellule, 18, 313 (1901). 



2. Kogl, F., Ber., 68, 16 (1935); Kogl, F., and Tonnis, B., Z. physiol. Chem., 242, 



43 (1936). 



3. Kogl, F., Proc. Roy. Soc. (London), B124, 1 (1937); Kogl, F., Chem. and Ind., 



57, 49 (1938). 



4. du Vigneaud, V., Hofmann, K, Melville, D. B., and Gyorgy, P., /. Biol. Chem,., 



140, 643 (1941); Gyorgy, P., Rose, C. S., Hofmann, K., Melville, D. B., and 

 du Vigneaud, V., Science, 92, 609 (1940). 



5. Melville, D. B., Hofmann, K, Hague, E., and du Vigneaud, V., J. Biol. Chem., 



142, 615 (1942). 



