β-Hairpin Folding by NMR

Our lab has developed model systems for exploring the thermodynamic forces which drive parallel β-sheet structure in water. Parallel β-sheet are poorly understood despite being one of only three fundamental secondary structures. Analogous systems have been used to quantitatively explore how strand length, strand number and side-chain pairing affect stability in anti-parallel β-sheets. These studies are fundamental to understanding both protein folding, and designing multifunctional organocatalysts. Multi-dimensional NMR is used extensively to analyze folding and to generate solution structures of our peptides.1-3

We are currently working on understanding how strand length affects parallel β-sheet stability, and would like to explore how strand number and side-chains interactions influence folding. We would also like to gain further insight into thermodynamic differences between parallel and anti-parallel β-sheets. By combining these different factors, we hope to gain important insight on how β-sheet structure is formed in nature.

 

1. Syud, F. A.; Stanger, H. E.; Gellman, S. H. J. Am. Chem. Soc. 2001, 123, 8667.

2. Stanger, H. E.; Syud, F. A.; Espinosa, J. F.; Giriat, I.; Muir, T.; Gellman, S. H. PNAS 2001, 98, 12015.

3. Fisk, J. D.; Schmitt, M. A.; Gellman, S. H.  J. Am. Chem. Soc. 2006, 128, 7148.

4. Friere, F.; Fisk, J.D.; Peoples, A.J.; Ivancic, M.; Guzei, I.A.; Gellman, S.H. J. Am. Chem. Soc. 2008, 130, 7839.

5. Freire, F.; Gellman, S.H. J. Am. Chem. Soc. 2009, 131, 7970.