title: Structural Dimorphism of Achiral α,γ-Hybrid Peptide Foldamers: Coexistence of 12- and 15/17-Helices.
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.
authors.affiliation: Department of Chemistry, Indian Institution of Science Education and Research, Dr. Homi Bhabha Road, Pune, 411021, India.
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Misra
authors.affiliation: Department of Chemistry, Indian Institution of Science Education and Research, Dr. Homi Bhabha Road, Pune, 411021, India.
authors.forename: Abhijith
authors.initials: A
authors.lastname: Saseendran
authors.affiliation: NMR Research Center, Indian Institute of Science, Bangalore, 560012, India.
authors.forename: Gijo
authors.initials: G
authors.lastname: George
authors.affiliation: Department of Chemistry, Indian Institution of Science Education and Research, Dr. Homi Bhabha Road, Pune, 411021, India.
authors.forename: Kuruva
authors.initials: K
authors.lastname: Veeresh
authors.affiliation: Department of Physical Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai, 625 021, India.
authors.forename: K Muruga Poopathi
authors.initials: KM
authors.lastname: Raja
authors.affiliation: NMR Research Center, Indian Institute of Science, Bangalore, 560012, India.
authors.forename: Srinivasarao
authors.initials: S
authors.lastname: Raghothama
authors.affiliation: Institute of Biochemistry, Faculty of Biosciences, Pharmacy and Psychology, Talstraße 33, 04103, Leipzig, Germany.
authors.forename: Hans-Jörg
authors.initials: HJ
authors.lastname: Hofmann
authors.affiliation: Department of Chemistry, Indian Institution of Science Education and Research, Dr. Homi Bhabha Road, Pune, 411021, India.
authors.forename: Hosahudya N
authors.initials: HN
authors.lastname: Gopi
mesh_terms: D015119:Aminocaproic Acid / Q000737:chemistry*; D000621:Aminoisobutyric Acids / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D000072756:Protein Conformation, alpha-Helical; D017510:Protein Folding; D013237:Stereoisomerism
chemical_list: D000621:Aminoisobutyric Acids; D010455:Peptides; D015119:Aminocaproic Acid
keywords: X-ray diffraction; amino acids; foldamers; helical structures; molecular dynamics