The thorough understanding of weak secondary interactions is of utmost importance for controlling molecular recognition processes, which play a pivotal role in chemistry and biology. Such weak chemical forces commonly act in a cooperative manner providing an overall stability despite the weakness of each individual force involved. As part of the ongoing investigation we study the impact of an individual hydrogen bond using a �-hairpin peptide model system. This motif is common in proteins and is also interesting for drug discovery. �-Hairpins have been used as inhibitors of protein-protein interactions, for example [1]. By comparative investigation of strategically designed cyclic peptides, we describe the behavior of a specific weak interaction as part of a larger cooperative complex, in a biological-like context. Our combined computational and NMR spectroscopic ensemble analysis (NAMFIS) provides quantitative evidence for the influence of a specific, weak interaction force in a cooperatively folding �-hairpin[2]. Figure 1.  The folded conformations of reference peptide (green) and peptide capable of interstrand hydrogen bonding (blue). Amino acid side chains are shown for the interaction but are omitted for clarity in all other positions.References [1]Fasan R.; Dias R. L. A.; Moehle K.; Zerbe O.; Obrecht D.; Mittl P. R. E.; Gr�tter M. G.; Robinson J. A. ChemBioChem, 2006  , 7, 515-526.[2]Danelius E.; Brath U.; Erd�lyi M. Synlett, 2013  , 24, 2407-2410.

Solution NMR investigations of weak interactions using peptidomimetic templates

248th National Meeting (2014)

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