Dataset Information

Comparison of design strategies for promotion of beta-peptide 14-helix stability in water.

ABSTRACT: Many short beta-peptides adopt well-defined conformations in organic solvents, but specialized stabilizing elements are required for folding to occur in aqueous solution. Several different strategies to stabilize the 14-helical secondary structure in water have been developed, and here we provide a direct comparison of three such strategies. We have synthesized and characterized beta-peptide heptamers in which variously a salt bridge between side chains, a covalent link between side chains, or two cyclically constrained residues have been incorporated to promote 14-helicity. The incorporation of a salt bridge does not generate significant 14-helicity in water, according to CD and 2D NMR data. In contrast, incorporation either of a lactam bridge between side chains or of cyclic residues results in stable 14-helices in water. The beta-peptides featuring trans-2-aminocyclohexanecarboxylic acid (ACHC) residues show the highest 14-helical backbone stability, with hardly any sensitivity to pH or ionic strength. The beta-peptides featuring side-chain-to-side-chain cyclization show lower 14-helical backbone stability and higher sensitivity to pH and ionic strength, but increased order between the side chains because of the cyclization.

SUBMITTER: Vaz E

PROVIDER: S-EPMC3551619 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Comparison of design strategies for promotion of beta-peptide 14-helix stability in water.

Vaz Esther E Pomerantz William C WC Geyer Matthias M Gellman Samuel H SH Brunsveld Luc L

Chembiochem : a European journal of chemical biology 20080901 14

Many short beta-peptides adopt well-defined conformations in organic solvents, but specialized stabilizing elements are required for folding to occur in aqueous solution. Several different strategies to stabilize the 14-helical secondary structure in water have been developed, and here we provide a direct comparison of three such strategies. We have synthesized and characterized beta-peptide heptamers in which variously a salt bridge between side chains, a covalent link between side chains, or t ...[more]

PMID: 18756554

Similar Datasets

Project description:Collagen-like peptides (CLP) are multifunctional materials garnering a lot of recent interest from the biomaterials community due to their hierarchical assembly and tunable physicochemical properties. In this work, we present a computational study that links the design of CLP heterotrimers to the thermal stability of the triple helix and their self-assembly into fibrillar aggregates and percolated networks. Unlike homotrimeric helices, the CLP heterotrimeric triple helices in this study are made of CLP strands of different chain lengths that result in 'sticky' ends with available hydrogen bonding groups. These 'sticky' ends at one end or both ends of the CLP heterotrimer then facilitate inter-helix hydrogen bonding leading to self-assembly into fibrils (clusters) and percolated networks. We consider the cases of three sticky end lengths - two, four, and six repeat units - present entirely on one end or split between two ends of the CLP heterotrimer. We observe in CLP heterotrimer melting curves generated using coarse grained Langevin dynamics simulations at low CLP concentration that increasing sticky end length results in lower melting temperatures for both one and two sticky ended CLP designs. At higher CLP concentrations, we observe non-monotonic trends in cluster sizes with increasing sticky end length with one sticky end but not for two sticky ends with the same number of available hydrogen bonding groups as the one sticky end; this nonmonotonicity stems from the formation of turn structures stabilized by hydrogen bonds at the single, sticky end for sticky end lengths greater than four repeat units. With increasing CLP concentration, heterotrimers also form percolated networks with increasing sticky end length with a minimum sticky end length of four repeat units required to observe percolation. Overall, this work informs the design of thermoresponsive, peptide-based biomaterials with desired morphologies using strand length and dispersity as a handle for tuning thermal stability and formation of supramolecular structures.

Dataset Information

Comparison of design strategies for promotion of beta-peptide 14-helix stability in water.

Publications

Comparison of design strategies for promotion of beta-peptide 14-helix stability in water.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets