Structural Dimorphism of Achiral α, γ‐Hybrid Peptide Foldamers: Coexistence of 12‐ and 15/17‐Helices. Issue 15 (14th February 2017)

• Record Type: Journal Article
• Authors: Misra, Rajkumar; Saseendran, Abhijith; George, Gijo; Veeresh, Kuruva; Raja, K. Muruga Poopathi; Raghothama, Srinivasarao; Hofmann, Hans‐Jörg; Gopi, Hosahudya N.
• Is Part Of: Chemistry. Volume 23:Issue 15(2017)
• Page Start: 3764
• Page End: 3772
• Publication Date: 2017-02-14
• Subjects: amino acids -- foldamers -- helical structures -- molecular dynamics -- X-ray diffraction; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201605753
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: 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. Abstract : Twisting this way or that : Single‐crystal and solution conformations of hybrid peptides composed of achiral α‐aminoisobutyric acid (Aib) and 4, 4‐dimethyl‐substituted 4‐aminoisocaproic acid (Aic) residues in 1:1 alternation showed 12‐ and 15/17‐helical folds, depending on the sequence length (see figure). Quantum chemical calculations support the experimental data and suggest the possibility of an equilibrium between helix types.