Structural Dimorphism of Achiral α,γ-Hybrid Peptide Foldamers: Coexistence of 12- and 15/17-Helices

Rajkumar Misra, Abhijith Saseendran, Gijo George, Kuruva Veeresh, K. Muruga Poopathi Raja, Srinivasarao Raghothama, Hans Jörg Hofmann*, Hosahudya N. Gopi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Here, novel 12-helices in α,γ-hybrid peptides composed of achiral α-aminoisobutyric acid (Aib) and 4-aminoisocaproic acid (Aic, doubly homologated Aib) monomers in 1:1 alternation are reported. The 12-helices were indicated by solution and crystal structural analyses of tetra- and heptapeptides. Surprisingly, single crystals of the longer nonapeptide displayed two different helix types: the novel 12-helix and an unprecedented 15/17-helix. Quantum chemical calculations on both helix types in a series of continuously lengthened Aib/Aic-hybrid peptides confirm that the 12-helix is more stable than the 15/17-helix in shorter peptides, whereas the 15/17-helix is more stable in longer sequences. Thus, the coexistence of both helix types can be expected within a definite range of sequence lengths. The novel 15/17- and 12-helices in α,γ-hybrid peptides with 5→1 and 4→1 hydrogen-bonding patterns, respectively, can be viewed as backbone-expanded analogues of native α- and 310-helices.

Original languageEnglish
Pages (from-to)3764-3772
Number of pages9
JournalChemistry - A European Journal
Issue number15
StatePublished - 13 Mar 2017
Externally publishedYes


  • X-ray diffraction
  • amino acids
  • foldamers
  • helical structures
  • molecular dynamics


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