title: Aza-Glycine Induces Collagen Hyperstability.
abstract: Hydrogen bonding is fundamental to life on our planet, and nature utilizes H-bonding in nearly all biomolecular interactions. Often, H-bonding is already maximized in natural biopolymer systems such as nucleic acids, where Watson-Crick H-bonds are fully paired in double-helical structures. Synthetic chemistry allows molecular editing of biopolymers beyond nature's capability. Here we demonstrate that substitution of glycine (Gly) with aza-glycine in collagen may increase the number of interfacial cross-strand H-bonds, leading to hyperstability in the triple-helical form. Gly is the only amino acid that has remained intolerant to substitution in collagen. Our results highlight the vital importance of maximizing H-bonding in higher order biopolymer systems using minimally perturbing alternatives to nature's building blocks.
authors.affiliation: Department of Chemistry, University of Pennsylvania , 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, United States.
authors.forename: Yitao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, University of Pennsylvania , 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, United States.
authors.forename: Roy M
authors.initials: RM
authors.lastname: Malamakal
authors.affiliation: Department of Chemistry, University of Pennsylvania , 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, United States.
authors.forename: David M
authors.initials: DM
authors.lastname: Chenoweth
mesh_terms: D001372:Aza Compounds / Q000737:chemistry*; D003094:Collagen / Q000737:chemistry*; D005998:Glycine / Q000737:chemistry*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D055550:Protein Stability
chemical_list: D001372:Aza Compounds; D010455:Peptides; D003094:Collagen; D005998:Glycine