Reactivity of PNA Thioesters in Chemical Ligation Reactions

Abstract

The ligation rate and efficiency of PNA thioesters in the reaction with the pentapeptide CRYNK has been determined and proved to be substantially lower in comparison with the corresponding C-terminal glycine thioester.

native chemical ligation - thioesters - peptide nucleic ­acid - reactivity - convergent synthesis

References

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10 Apart from this, side-reactions were observed with the ligation of Lys-thioesters (see ref. 4c) and at Asp-Cys and Glu-Cys sites. See: Villain M. Gaertner H. Botti P. Eur. J. Org. Chem.  2003,  17:  3267 

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13

MS: m/z found (calculated) for:
Compound 6: [M + H⁺]: 1340.9 (1340.5), [M + 2 H⁺]: 670.9 (670.8).
Compound 7: [M + H⁺]:1283.6 (1283.5), [M + 2 H⁺]: 642.6 (642.3).
Compound 8: [M + H⁺]: 1308.5 (1308.3), [M + 2 H⁺]: 655.2 (654.7).
Compound 10: [M + H⁺]: 1847.1 (1846.2), [M + 2 H⁺]: 923.9 (923.6), [M + 3 H⁺]: 616.2 (616.1).
Compound 11: [M + H⁺]: 1788.9 (1788.8), [M + 2 H⁺]: 895.2 (894.9).
Compound 12: [M + H⁺]: 1815.2 (1814.8), [M + 2 H⁺]: 907.8 (907.9), [M + 3 H⁺]: 605.7 (605.6).

14

On the basis of similar studies to assess the ligation efficiency of amino acid thioesters (see ref. 9) the pentapeptide CRANK was initially used. However, it proved to be impossible to resolve the PNA-conjugate of this peptide and the starting PNA thioester on RP-HPLC column.