Ligation strategies

Fig. 8. Typical examples of calyx sugars prepared through various ligation strategies.

JP Tam, Q Yu. Methionine ligation strategy in the biomimetic synthesis of parathyroid hormones. Biopolymers 46, 319, 1998. 

JP Tam, A Yu, A Miao. Orthogonal ligation strategies for peptide and protein synthesis. Biopolymers (Pept Sci) 51, 311-332, 1999. 

Shogren-Knaak, M.A., Fry, C.J. and Peterson, C.L. (2003) A native peptide ligation strategy for deciphering nudeosomal histone modifications. The Journal of Biological Chemistry, 278, 15744-15748. 

Scheme 1 Examples of Chemoselective Ligation Strategies Resulting in the Formation of Nonpeptidic Bonds (a) Hydrazone, (b) Oxime, (c) Thiazolidine...

Peptide ligation strategies used so far have mainly been used for protein total synthesis and protein engineering purposes. The ability to prepare perfectly mono-disperse and relatively high molar mass peptides with precise control over the a-amino acid sequence could also afford unprecedented opportunities for the development of novel biologically-inspired supramolecular architectures and materials. As a final, recent, example, the preparation of a protein[2]catenane using NCL is shown in Figure 6.6.5 [34]. 

The chemical ligation strategy has been applied primarily to the formation of bonds involving cysteine and homocysteine the latter residue can be converted into methionine by methylation. Moreover, the number of examples of this approach is rather limited and side reactions have been noted which will probably be unique for individual polypeptides. Nevertheless, this strategy would appear to have great potential in the chemical synthesis of long polypeptides. Section 4.1.5 extensively discusses the chemical ligation field. 

Recently, another cysteine-free ligation strategy has been reported for the synthesis of glycopeptides. The method, dubbed sugar assisted ligation (SAL), utilizes a peptide thioester and a glycopeptide in which the carbohydrate is derivatized with a thiol auxiliary at the C-2 acetamide [52,53]. The proposed mechanism of this ligation, depicted in Scheme 7, involves... 

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