Hydrolytic Cleavage of Pyroglutamyl-Peptide Bond. IV. Highly Selective Cleavage of Thyrotropin Releasing Hormone (TRH) in Aqueous Methanesulfonic Acid

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The acid hydrolysis of thyrotropin releasing hormone (TRH) (pGlu-His-Pro-NH_2) in various acids under several conditions and the highly selective cleavage of the pGlu-His bond are described. First, the decomposition of TRH in dilute acid was studied. The incubation of TRH in 1 N HCl at 60℃ resulted in the formation of eleven hydrolysates, H-Glu-His-Pro-NH_2,H-Glu-His-Pro-OH, H-His-Pro-NH_2,H-His-Pro-OH, His-Pro diketopiperazine, pGlu-His-Pro-OH, pGlu-His-OH, H-Glu-His-OH, H-Pro-His-OH, pGlu-OH and H-Glu-OH. The results showed that the pGlu-His linkage and pGlu moiety were more sensitive than the C-terminal carboxamide to the acid hydrolysis. Then, a simple means of deblocking pGlu-peptide was applied to TRH. The hydrolysis of TRH in 70% methanesulfonic acid (MSA) at 25℃ produced H-His-Pro-NH_2 and H-His-Pro-OH as major products, and H-Glu-His-Pro-NH_2,the diketopiperazine and pGlu-His-Pro-OH as minor products. The 90% MSA hydrolysis at 25℃ was highly selective for the cleavage product (H-His-Pro-NH_2) of the pGlu-His bond, without affording the ring-opened products (H-Glu-His-Pro-NH_2 and H-Glu-His-Pro-OH). The yield of deamidated products (H-His-Pro-OH and pGlu-His-Pro-OH) was less than 3% after 3 d.
公益社団法人日本薬学会の論文
1997-01-15