Solid-state NMR structural characterization of self-assembling peptide analogues

Solid-state NMR;Peptide analogue;Peptoid nanosheet;Low molecular weight gelator

Hudson, Benjamin Cole ; Paravastu, Anant K. Chemical and Biomolecular Engineering Champion, Julie Bommarius, Andreas Grover, Martha Lieberman, Raquel ; Paravastu, Anant K.

University:Georgia Institute of Technology

Department:Chemical and Biomolecular Engineering

关键词: Solid-state NMR;    Peptide analogue;    Peptoid nanosheet;    Low molecular weight gelator;   

Others  :  https://smartech.gatech.edu/bitstream/1853/62215/1/HUDSON-DISSERTATION-2018.pdf

美国|英语

来源: SMARTech Repository

【 摘 要 】

Research in the field of designer nanostructure has shown great potential for use of peptides, peptide analogues, and a wide array of small molecules in a variety of industries and applications. As the field continues to expand, the need for techniques which are capable of providing structural detail at atomic-level resolution will only grow. The question of how best to extract atomic-level structural detail from these systems has yet to be adequately addressed, however. Here I show the efficacy of solid-state nuclear magnetic resonance (NMR) in extracting molecular-level detail from two self-assembling peptide analogues: peptoid B28 and fluorenylmethoxycarbonyl-diphenylalanine (Fmoc-FF). A study of peptoid B28 nanosheets has shown the capability of dipolar recoupling solid-state NMR to distinguish between the cis and trans configurations of peptoid backbone amide bonds, providing refined physical constraints for an evolving B28 nanosheet molecular model and revealing previously unconsidered peptoid backbone folding behavior. My study of Fmoc-FF suggests this system is highly polymorphic despite its small size, and that the polymorphism appears to be dependent on solvent environment. Despite this polymorphism however, two-dimensional solid-state NMR indicates each of our Fmoc-FF systems feature a common backbone hydrogen-bonding pattern of diphenylalanine sidechains inconsistent with the most widely accepted Fmoc-FF nanofiber model.Solid-state NMR has never been applied either peptoid B28 or Fmoc-FF, nor is there any evidence in the literature that it has ever been applied a peptoid system or Fmoc-dipeptide. I am borrowing these solid-state NMR experiments from peptide characterization methods and applying them to probe for structural phenomena that has never been tested in either system. I have simply looked at the proposed molecular arrangements in both peptoid B28 and Fmoc-FF and applied measurements sensitive to the details I want to see. This is a not a standard application of solid-state NMR, but nothing new ever began as standard.