Peptoids (i.e. N-substituted glycine oligomers) developed in the early 1990s are structurally related to peptides with the side chains located on the amide nitrogen rather than on the α-carbon.[1] Peptoids are well-suited peptidomimetics since they possess undeniable advantages such as proteolytic stability and cost-effective synthesis with a great potential for diversity.[2] However, peptoids are inherently more flexible than peptides due to the absence of internal hydrogen bonding, achiral backbone and N,N-disubstituted amides which can populate both cis and trans conformations. This intrinsic flexibility could in fact be turned into a key advantage to access different type of folded architectures. A set of specific side chains capable of forming local interactions with the backbone to improve folding propensities of peptoids are currently developed in our group.[3] These tools open the way for the design of well-structured functionalized biomimetics such as cationic amphipathic helical peptoids with bactericidal activities.[4]
References
1. R. J. Simon, R. S. Kania, R. N. Zuckermann, V. D. Huebner, D. A. Jewell, S. Banville, S. Ng, L. Wang, S. Rosenberg, D. C. Spellmeyer, R. Tan, A. D. Frankel, D. V. Santi, F. E. Cohen, P. A. Bartlett, Proc. Natl. Acad. Sci. USA 1992, 89, 9367.
2. R. Zuckermann and T. Kodadek, Curr. Opin. Mol. Ther. 2009, 11, 299.
3. (a) C. Caumes, O. Roy, S. Faure, C. Taillefumier, J. Am. Chem. Soc. 2012, 134, 9553; (b) O. Roy, G. Dumonteil, S. Faure, L. Jouffret, A. Kriznik, C. Taillefumier, J. Am. Chem. Soc. 2017, 139, 13533.
4. R. Shyam, N. Charbonnel, A. Job, C. Blavignac, C. Forestier, C. Taillefumier, S. Faure, ChemMedChem 2018, 15, 1513.
Contact local IBMM : Dr. Thomas-Xavier Métro, C.R. CNRS (DAPP)