Backbone Thioester Exchange

Thioester exchange1 is a method developed for evaluating higher order structural stability in small folded peptides or proteins. The approach involves incorporation of a thioester bond into a polypeptide chain. The thioester containing peptide (C) can participate in a transthioesterification reaction with a competing thiol (D) to derive insight on the conformational stability of the thioester-containing analogue in its native state (see cartoon).


  1. 1.KTE can be quantified by HPLC or 19F-NMR
  2. 2.Kfold = KTE - 1 (Reference 1)
  3. 3.∆Gfold = -RT ln(Kfold)



1. Woll, M. G.; Gellman, S.H. J. Am. Chem. Soc. 2004, 126, 11172.

2. Hadley, E. B.; Witek, A. M.; Freire, F.; Gellman, S. H. Angew. Chem. Int. Ed. 2007, 46, 7056.

3. Hadley, E. B.; Gellman, S. H. J. Am. Chem. Soc. 2006, 128, 16444.

4. Hadley, E. B.; Testa, O. D.; Woolfson, D. N.; Gellman, S. H. Proc. Nat. Acad. Sci. USA 2008, 105, 530.

5. Steinkruger, J.D.; Woolfson, D.N.; Gellman, S.H. Manscript in preparation.