SFPE5 STRUCTURE: 19F-1H NOE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Oligomers of N-substituted glycines, or peptoids, are an important class of non-native polymers whose close structural similarity to natural a-peptides and ease of synthesis offer significant advantages for the study of biomolecular interactions and the development of biomimetics. Peptoids that are N-substituted with a-chiral aromatic amide side chains have been shown to adopt stable helical conformations reminiscent of the polyproline type-I helix. Elucidation of the factors involved in peptoid helix formation is essential for the development of general rules for the design of peptoids with discreet and novel structures. Here, we investigate the effects of pentafluorophenyl functionality on the conformational profiles of the peptoid helix. This work is enabled by the synthesis of a new a-chiral amine building block, (S)-1-(pentafluorophenyl)ethylamine (S-2), that was found to be highly compatible with peptoid synthesis (delivering (S)-N-(1-(pentafluorophenyl)ethyl)glycine oligomers). The strategic incorporation of this perfluorinated monomer unit is allowing us to probe both the potential for ?-stacking interactions along the side of peptoid helices and the role of side chain electrostatics in peptoid folding. Initial studies revealed that (S)-N-(1-(pentafluorophenyl)ethyl)glycine monomers stabilize helical peptoid structures at significantly shorter lengths relative to non-fluorinated peptoid analogues.