title: Secondary structure of short β-peptides as the chiral expression of monomeric building units: a rational and predictive model.
abstract: Chirality of the monomeric residues controls and determines the prevalent folding of small oligopeptides (from di- to tetramers) composed of 2-aminocyclobutane-1-carboxylic acid (ACBA) derivatives with the same or different absolute and relative configuration. The cis-form of the monomeric ACBA gives rise to two conformers, namely, Z6 and Z8, while the trans-form manifests uniquely as an H8 structure. By combining these subunits in oligo- and polypeptides, their local structural preference remains, thus allowing the rational design of new short foldamers. A lego-type molecular architecture evolves; the overall look depends only on the conformational properties of the structural building units. A versatile and efficient method to predict the backbone folds of designed cyclobutane β-peptides is based on QM calculations. Predictions are corroborated by high-resolution NMR studies on selected stereoisomers, most of them being new foldamers that have been synthesized and characterized for the first time. Thus, the chiral expression of monomeric building units results in the defined secondary structures of small oligomers. As a result of this study, a new set of chirality controlled foldamers is provided to probe as biocompatible biopolymers.
authors.affiliation: Departament de Química, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Gorrea
authors.forename: Gábor
authors.initials: G
authors.lastname: Pohl
authors.forename: Pau
authors.initials: P
authors.lastname: Nolis
authors.forename: Sergio
authors.initials: S
authors.lastname: Celis
authors.forename: Kepa K
authors.initials: KK
authors.lastname: Burusco
authors.forename: Vicenç
authors.initials: V
authors.lastname: Branchadell
authors.forename: András
authors.initials: A
authors.lastname: Perczel
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Ortuño
mesh_terms: D000598:Amino Acids, Cyclic / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009842:Oligopeptides; D010455:Peptides / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013237:Stereoisomerism
chemical_list: C541323:2-aminocyclobutane-1-carboxylic acid; D000598:Amino Acids, Cyclic; D009842:Oligopeptides; D010455:Peptides