|Name||Mr. Matthew Sarnowski|
|Organization or Institution||University of South Florida|
Synthesis and Conformational Analysis of N-Amino Peptides
M. P. Sarnowski, C. Kang, Y. M. Elbatrawi, L. Wojtas, and J. R. Del Valle*
University of South Florida
The introduction of backbone amide substituents has a profound impact of the conformation and stability of host peptides. Recently, we reported the synthesis of diverse chiral α-hydrazino acids that can be chemoselectively incorporated into a growing peptide chain on solid support to afford N-amino peptides (NAPs). We reasoned that the propensity of these residues to participate in hydrogen bonding could be exploited to enforce intramolecular interactions that yield stabilized extended structures. Here, we describe the synthesis and conformational analysis of β-hairpin model peptides featuring backbone amination. NMR, CD, computational and thermodynamic analysis demonstrate the unique ability of NAPs to stabilize β-sheet conformation. Sheet-like structures featuring intraresidue C6 H-bonds were observed in the X-ray crystal structure of a NAP dimer, which to our knowledge represents the first structure of this type reported for N-substituted peptides. These results suggest that backbone amination promotes β-sheet folding by controlling both local backbone geometries and longer-range intermolecular interactions.