ANALOGUES 



the growth of bacteria by competition with aneurine led to the dis- 

 covery *® that several thiol derivatives of thiazole were bacteriostatic, 

 but the inhibition was not reversed on addition of aneurine. In fact, 

 the bacteriostatic activity appeared to be a function of the thiol 

 group rather than of the thiazole ring, and quite unconnected with 

 aneurine requirements. 



General Conclusions 



The data summarised above on the vitamin B^ activity of com- 

 pounds related to aneurine has an obvious bearing on the question of 

 enzyme specificity. The first generalisation that can be made — and 

 this will be evident also from the discussion of the functions of other 

 members of the vitamin B complex — is that specificity is not absolute ; 

 there is generally a group of compounds, the activity of which increases 

 to a maximum with one particular member. As it happens, maximum 

 vitamin B^ activity is not exhibited by the compound that Nature 

 chose to use for this purpose, but by the next higher homologue. This 

 is admittedly unusual. The second generalisation is that activity is 

 confined to the compounds comprising a thiazole ring and a pyrimidine 

 ring linked together at specific points by a chain of one or two carbon 

 atoms. Compoimds that are linked directly are inactive, suggesting 

 that a certain freedom of movement of the molecule is essential. The 

 third generalisation is that the presence of a hydroxyl group in the 

 side-chain attached to the thiazole ring is essential for activity, 

 obviously because without it no pyrophosphate could be formed. This 

 must be a primary alcohol group, but the side-chain can apparently 

 contain three carbon atoms, although optimal activity is obtained 

 with two. Fourthly, one amino group in the pyrimidine ring, and 

 only one, is essential, and this is preferably a primary group. A 

 quaternary nitrogen atom in the thiazole ring is also essential. Fifthly, 

 the nature of the alkyl groups attached to both rings is important ; 

 optimal activity was exhibited by compounds in which these together 

 amounted to two or three carbon atoms, and fell progressively as the 

 number increased. 



The antagonistic action of pyrithiamine, neopyrithiamine and 

 oxy thiamine are highly significant, as, although they have no vitamin 

 Bi activity, they appear to be capable of displacing aneurine from 

 attachment to the protein of the enzjnne molecule. It has been 

 customary to picture the attachment of a molecule at the surface of 

 an enzyme as taking place at a particular point, but the theory ad- 

 vanced by Linus Pauling to explain the formation of anti-bodies 

 suggests that contact is more probably over a particular area rather 

 than at a point. 



9 129 



