Purines. XIV. Selective Removal of N-Terminal Amino Acids from Peptides by the Use of Purin-6-yl Group at the N-Terminus

抄録

Introduction of the purin-6-yl group into oligopeptides IIa-f on the N-terminal nitrogen was effected by treating them with 6-chloropurine in boiling aq. 1-butanol containing triethylamine or in H₂O containing one eq. mole of NaOH at 90°. The yields of the purinylated peptides (IIIa-f) were 8-73%. Similar condensations of 4-chloro-6-methylpyrimidine with IIa and with glycine provided XII and XIII. In alternative synthesis of IIIa, d, e, (purin-6-yl) amino acids IVa and IVb were coupled with ethyl glycinate or glycylglycinate by the dicyclohexylcarbodiimide method, followed by hydrolysis of the resulting esters VIIIa, b, c. Condensation of α-naphthylamine with ethyl N-chloroacetylglycinate and alkaline hydrolysis of the product furnished N-(α-naphthyl)-glycylglycine (X). Next the hydrolyses of dipeptides IIa, b, c, IIIa, b, c, X, and XII in boiling H₂O at various pH's were examined. At pH 7 all dipeptides were practically stable for at least 10 hr, but at pH 13 they were hydrolyzed at various rates. At pH 1 N-substituted dipeptides IIIa, b, c, X, and XII suffered hydrolysis more rapidly than did the parent dipeptides (IIa, b, c). Among the glyoylglycine derivatives, purinyl derivative IIIa was hydrolyzed most rapidly. At pH 4 purinyl derivatives IIIa, b, c only underwent hydrolysis, whereas the other dipeptides remained unchanged even after 10 hr's reflux. In the hydrolyses of the N-purinylated tri-(IIId, e) and tetrapeptides (IIIf) in H₂O at pH 4 and 100° for 5 hr, the N-terminal residues were almost selectively disconnected to the extent of 21-78%. It is suggested that the observed assistance of the purinyl substituent in hydrolytic cleavage of the N-terminal peptide bond is intramolecular in nature.