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Foldamers as versatile frameworks for the design and evolution of function

Nature Chemical Biology volume 3, pages 252–262 (2007)Cite this article

Abstract

Foldamers are sequence-specific oligomers akin to peptides, proteins and oligonucleotides that fold into well-defined three-dimensional structures. They offer the chemical biologist a broad pallet of building blocks for the construction of molecules that test and extend our understanding of protein folding and function. Foldamers also provide templates for presenting complex arrays of functional groups in virtually unlimited geometrical patterns, thereby presenting attractive opportunities for the design of molecules that bind in a sequence- and structure-specific manner to oligosaccharides, nucleic acids, membranes and proteins. We summarize recent advances and highlight the future applications and challenges of this rapidly expanding field.

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Figure 1
Figure 2: The 14-helix conformation.
Figure 3: 14-helix and mixed α/β-helices.
Figure 4: Design principles for foldamer scaffolds.
Figure 5: Self-associating foldamer.
Figure 6: Downsizing a natural host defense peptide.
Figure 7: Simultaneous parallel and antiparallel hydrophobic packing.

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  1. Catherine M Goodman & Sungwook Choi

    Present address: Present addresses: Nature Publishing Group, 25 First St. Suite 104, Cambridge, Massachusetts 02141, USA (C.M.G.) and The Skaggs Institute for Chemical Biology, Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, San Diego, California 92130, USA (S.C.),

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  1. Department of Biochemistry and Biophysics, University of Pennsylvania, School of Medicine, 422 Curie Boulevard, Philadelphia, 19104-6059, Pennsylvania, USA

    Catherine M Goodman, Sungwook Choi, Scott Shandler & William F DeGrado

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Correspondence to William F DeGrado.

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W. DeGrado is named on patents for antimicrobial and antiheparin foldamers. These patents are held by the University of Pennsylvania and licensed to PolyMedix.

Supplementary information

Supplementary Fig. 1

Model of the interaction between a designed arylamide (smMLCK mimic) and calmodulin. (PDF 56 kb)

Supplementary Table 1

Interactions of non-natural foldamers with biological targets. (PDF 57 kb)

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Goodman, C., Choi, S., Shandler, S. et al. Foldamers as versatile frameworks for the design and evolution of function. Nat Chem Biol 3, 252–262 (2007). https://doi.org/10.1038/nchembio876

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