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.

Recent Publications:

7. "Impact of Strand Number on Parallel β-Sheet Stability." Kung, V.M.; Cornilescu, G.; Gellman, S.H. Angew. Chem. Int. Ed. Engl. 2015, 54,14336–14339.

6. “Impact of Strand Length on the Stability of Parallel-β-Sheet Secondary Structure.” Freire, F.; Almeida, A.M.; Fisk, J.D.; Steinkruger, J.D.; Gellman, S.H., Angew. Chem. Int. Ed. Engl. 2011, 50, 8735-8.

5.  "Macrocyclic Design Strategies for Small, Stable Parallel β-Sheet Scaffolds," F. Friere and S. H. Gellman J. Am. Chem. Soc. 2009, 131, 7970.

4. "Diacid Linkers that Promote Parallel β-Sheet Secondary Structure in Water," F. Friere, J. D. Fisk, A. J. Peoples, M. Invancic, I. A. Guzei and S . H. Gellman J. Am. Chem. Soc. 2008, 130, 7839.

3. "Thermodynamic Analysis of Autonomous Parallel β-Sheet Formation in Water," J. D. Fisk, M. A. Schmitt and S. H. Gellman J. Am. Chem. Soc. 2006, 128, 7148.

2. "Length-Dependent Stability and Strand Length Limits in Antiparallel β-Sheet Secondary Structure," H. E. Stanger, F. A. Syud, J. F. Espinosa, I.G iriat, T. Muir and S. H. Gellman Proc. Natl. Acad. Sci. USA 2001, 98, 12015.

1. "Analysis of Interstrand Sidechain-Sidechain Contacts in a Designed β-Hairpin:  Significance of Both Lateral and Diagonal Interactions," F. A. Syud, H. E. Stanger and S. H. Gellman J. Am. Chem. Soc. 2001, 123, 8667.