ESR 2: Diana Gimenez-Ibanez: 31 March - 12 May 2017

Title: The Application of Fluorine as a Tool to Modulate Peptoid Conformation

Location: Molecular Foundry. Lawrence Berkeley National Laboratory, Berkeley, CA. (USA)

Accommodation: 2216 McGee Avenue, Berkeley, CA 94703, United States

Science: During the two previous years of development of the research project we have been focussed in the potential application of fluorine in order to design conformationally stable peptoid units. We hypothesized that by increasing the electron deficient character of aromatic groups it could actually be possible to design, for the first time, a peptoid monomer that displays a clear isomer preference based only on electronic factors negating the need for steric effects such as chiral alpha methyl groups. Our work to date has been further supported by X-Ray crystallographic studies and molecular dynamics (in collaboration with Professor Vincent Voelz at Temple University, US). As a result, encouragingly, we recorded some of the largest ever Kcis/trans values reported and demonstrated that fluorine has in all cases a major impact over the peptoid bond.

Given the highly promising data produced in the model systems, our focus has moved to the potential applicability of these new fluorinated monomers in order to control peptoid secondary structure in longer systems. With this purpose, we applied for a short stay secondment of ~1.5 month at the Molecular Foundry between 31st March-12th May. Within our visit to the LBNL, and thanks to the high throughput peptoid synthesizer, we have been able to synthetize a small library of fluorinated and non-fluorinated peptoids (~37 peptoids between fluorinated and non-fluorinated) incorporating our candidate monomers. All the poly-peptoids have been taken back to Durham, where we have started to perform the corresponding purification and initial characterization of the fluorinated candidates. We aim to be able to proceed to their biophysical characterization as or next step, being of remarkable interest the analysis of the secondary structure exhibited by the fluorinated oligomers (e.g. CD). Furthermore, we also expect to be able to perform some crystallographic X-Ray studies (structural cis/trans competition experiments between residues in cyclic structures) and 19F-NMR analysis of some fluorinated peptoid hexamers, that could be also successfully synthetized thanks to the Molecular Foundry User program.

New Skills acquired

Technical and Scientific Skills

  • Automated instrumentation for peptoid synthesis
  • New protocols for peptoid derivatization and cleavage
  • New protocols for peptoid coupling activation

Interpersonal Skills

  • Adaptation to a new working environment
  • Ability to efficiently communicate with researchers from different multidisciplinary areas