646 4. SULFHYDRYL REAGENTS 



alone cannot depress the reactivity too greatly. However, in addition the 

 hydrogen bond may bring an adjacent side chain into the region of the SH 

 group and this second steric factor may further reduce the reactivity. Ben- 

 esch and Benesch (1953) compared the peptides, phenacetyl-L-cysteinyl- 

 glycine (PCG) and phenacetyl-L-cysteinyl-D-valine (PCV), with respect to 

 the polarographic reduction of their mercaptides with mersalyl and Ag+, 

 and found that a relative suppression of the ability of the PCV SH group 

 to react with these reagents is evident. This was interpreted as due to the 

 steric interference of the isopropyl group of valine in PCV, brought into 

 the proximity of the SH group by hydrogen bonding, whereas in PCG there 

 is no such side chain. In proteins the interference may be even greater. 

 This concept thus involves both a reaction of the SH group and steric 

 factors. 



The hydrogen-bonded structures could further lose water to form more 

 stable thiazolidine or thiazoline rings. Linderstrom-Lang and Jacobsen 

 (1941) found that 2-methylthiazoline can hydrolyze under certain con- 

 ditions to release an SH group and a peptide linkage, such as occurs 

 during protein denaturation. Thus in a cysteine peptide, where the hy- 

 drogen bonding is now to the keto oxygen, the following structures can 

 be written: 



S— H 



/ \ 

 H,C O HX S 



Ri — HC— NH— C— R, R— HC— NH— C — Rs 



OH 

 H-bonded form Thiazolidine form 



H,C S 



"I I 



R — HC— N=C-R2 



Thiazoline form 



Such transformations have been more recently discussed by Calvin (1954) 

 in connection with the structure of glutathione and the reactivities of SH 

 groups in enzymes. Indirect evidence for these rings was obtained by com- 

 paring the absorption spectra of thiols with 2-methylthiazoline (although 

 at high acidity so that the situation near neutrality is still not clear). If 

 such structures occur in enzymes, they could unquestionably account for 

 unreactivity. 



