Munich Multiscale Biofabrication Network

Huc Lab

https://huc.cup.uni-muenchen.de/

Threading of a foldamer through a cyclic protein aggregate (molecular model).
Helical array of protein around a stack of foldamer helices (crystal structure)

As shown in nature by proteins and nucleic acids, molecular folding allows to position functional groups in space with atomic precision over nanometric distances and gives access to sophisticated functions. The Huc laboratory designs, fabricates and investigates foldamers: bioinspired synthetic macromolecules that also adopt well-defined folded shapes in the size-range of small proteins, but that are neither peptidic nor nucleotidic. Because functions rely on shape, and shape relies on chemical constitution, it is expected that artificial folded architectures may provide access to functions beyond those of proteins and nucleic acids.

A specific focus is to interface these nonnatural objects with their natural counter-parts in hybrid structures (Figures 1 & 2), laying the foundation of a kind of molecular bionics. Can natural and non-natural components be combined? Can a protein be amputated of part of its structure and then mended by a synthetic molecular prosthesis able to enhance its properties?

 

 

References

  1. C. G. Pappas, P. K. Mandal, B. Liu, B. Kauffmann, X. Miao, D. Komáromy, W. Hoffmann, C. Manz, R. Chang, K. Liu, K. Pagel, I. Huc, S. Otto, Emergence of low-symmetry foldamers from single monomers. Nat. Chem 2020, 12, 1180
  2. K. Ziach, C. Chollet, V. Parissi, P. Prabhakaran, M. Marchivie, V. Corvaglia, P. P. Bose, K. Laxmi-Reddy, F. Godde, J.-M. Schmitter, S. Chaignepain, P. Pourquier, I. Huc, Single helically folded aromatic oligoamides that mimic the charge surface of double-stranded B-DNA. Nat. Chem. 2018, 10, 511
  3. M. Rogers, S. Kwon, S. J. Dawson, P. K. Mandal, H. Suga, I. Huc, Ribosomal synthesis and folding of peptide-helical aromatic foldamer hybrids, Nat. Chem. 2018, 10, 405
  4. S. De, B. Chi, T. Granier, T. Qi, V. Maurizot, I. Huc, Designing cooperatively folded abiotic uni- and multimolecular helix bundles. Nat. Chem. 2018, 10, 51
  5. Q. Gan, X. Wang, B. Kauffmann, F. Rosu, Y. Ferrand, I. Huc, Translation of rod-like template sequences into homochiral assemblies of stacked helical oligomers. Nat. Nanotech. 2017, 12, 447