Synthesis and enzymic hydrolysis of cyclic peptides containing an anthranilic acid residue

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Abstract
Two cyclic peptides cyclo (Phe‐MeAnt‐Glyn) with MeAnt = 5‐methyl‐anthranilic acid residue, n = 4 (3b) and n = 6 (4b), have been synthesized in solution and their reaction with α‐chymotrypsin analyzed. The polyglycyl chain was prepared by the phosphazo method; cyclization at the Gly‐Phe site occurred in good yield using the azide method. Catalysis of the hydrolysis of peptides 3b and 4b by α‐chymotrypsin was characterized at 37° by the apparent second‐order rate constants kcat/Km 0.12 and 1.15 m‐1 s‐1, respectively, in agreement with the usual acceleration observed upon enlargement of the size of the peptidic ring in cyclic peptides. α‐Chymotrypsin specifically split the Phe‐MeAnt amide bond in cyclopeptide 4b. This specific orientation suggests that analogous structures with a functionalized methylene group instead of the methyl substituent can be used in the design of suicide substrates for serine proteases.