Thioester bonds Thioether

As simple as this methodology can be, it is not without a principal drawback. This is presented by the formation of an unnatural bond at the site of ligation between the two peptide segments. Such bonds include thioester- [25], oxime- [26], thioether- [27], disulfide- [28] and thiazole-forming [29] CL. These unnatural structures, however, are often well tolerated within the folded protein and examples exist of fully active protein molecules synthesized by CL [23]. 

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