Self-Healing Multiblock Copolypeptide Hydrogels via Polyion Complexation

Diblock, triblock, and pentablock copolypeptides were designed and prepared for formation of polyion complex hydrogels in aqueous media. Increasing the number of block segments was found to allow formation of hydrogels with substantially enhanced stiffness at equivalent concentrations. Use of similar length ionic segments also allowed mixing of different block architectures to fine-tune hydrogel properties. The pentablock hydrogels possess a promising combination of high stiffness, rapid self-healing properties, and cell compatible surface chemistry that makes them promising candidates for applications requiring injectable or printable hydrogel scaffolds

Homoallylglycine residues are superior precursors to orthogonally modified thioether containing polypeptides.

Homoallylglycine N-carboxyanhydride, Hag NCA, monomers were synthesized and used to prepare polypeptides containing Hag segments with controllable lengths of up to 245 repeats. Poly(l-homoallylglycine), GHA, was found to adopt an α-helical conformation, which provided good solubility in organic solvents and allowed high yield functionalization of its alkene side-chains via radical promoted addition of thiols. The conformations of these derivatives were shown to be switchable between α-helical and disordered states in aqueous media using thioether alkylation or oxidation reactions. Incorporation of GHA segments into block copolymers with poly(l-methionine), M, segments provided a means to orthogonally modify thioether side-chains different ways in separate copolypeptide domains. This approach allows preparation of functional polypeptides containing discrete domains of oxidized and alkylated thioether containing residues, where chain conformation and functionality of each domain can be independently modified

Modification of Poly(5,6-epoxy-l-norleucine) Gives Functional Polypeptides with Alternative Side-Chain Linkages.

The preparation and characterization of a new epoxide containing polypeptide, poly(5,6-epoxy-l-norleucine), via postpolymerization modification of poly(l-homoallylglycine) is described. Addition of thiols to the epoxide groups in poly(5,6-epoxy-l-norleucine) was studied as a means to prepare side-chain functional polypeptides. The solution properties of the derivatized polypeptides were studied in water and compared to similar thioether containing functional polypeptides prepared via different routes. Subtle differences in side-chain linkage chemistry were found to influence polypeptide solubility, chain conformation in solution, and thermoresponsive behavior. Poly(5,6-epoxy-l-norleucine) was found to be useful as a readily prepared intermediate that can be reacted with thiols to give a variety of functional polypeptides

Influence of Sulfoxide Group Placement on Polypeptide Conformational Stability.

The synthesis of a homologous series containing five new nonionic sulfoxide containing polypeptides was described. Sulfoxide groups bestowed water solubility for all homologues, which allowed their use as a model for study of helix-coil transitions in water while avoiding contributions from charged groups or phase separation. Polypeptides were found to adopt chain conformations in water that were dependent on distance of sulfoxides from chain backbones, overall side-chain lengths, and solvent. These results allow preparation of polypeptide segments with different chain conformations without changing chemical functionality for potential use in structural studies and functional applications

Self-Sorting Microscale Compartmentalized Block Copolypeptide Hydrogels

Multicomponent interpenetrating network hydrogels possessing enhanced mechanical stiffness compared to their individual components were prepared via physical mixing of diblock copolypeptides that assemble by either hydrophobic association or polyion complexation in aqueous media. Optical microscopy analysis of fluorescent-probe-labeled multicomponent hydrogels revealed that the diblock copolypeptide components rapidly and spontaneously self-sort to form distinct hydrogel networks that interpenetrate at micron length scales. These materials represent a class of microscale compartmentalized hydrogels composed of degradable, cell-compatible components, which possess rapid self-healing properties and independently tunable domains for downstream applications in biology and additive manufacturing

Tunable, Functional Diblock Copolypeptide Hydrogels Based on Methionine Homologs.

The preparation of new diblock copolypeptide hydrogels derived from homologs of l-methionine, that is, l-homomethionine and l-6-(methylthio)-l-norleucine is described. Compared to l-methionine residues, use of l-methionine homologs allow improved copolymerization with l-leucine residues to give well-defined block copolypeptides. These copolypeptides are subsequently modified using robust thioether alkylation reactions employing a variety of functional epoxides, which yield samples capable of forming transparent, self-healing hydrogels in water. The facile variation of different functional epoxides for postpolymerization modification is found to allow predictable functionalization and tuning of hydrogel properties by the modification of simple precursors

Polypeptide gels incorporating the exotic functional aromatic amino acid 4-amino-L-phenylalanine

High-molecular-weight polypeptides with functional aromatic side chains, poly(4-amino-l-phenylalanine), were prepared by the metal-initiated polymerization of the Nα-carboxyanhydride of the corresponding amino acid, which is a microbial derivative of phenylalanine

Influence of Sulfur-Containing Diamino Acid Structure on Covalently Crosslinked Copolypeptide Hydrogels.

Biologically occurring non-canonical di-α-amino acids were converted into new di-N-carboxyanhydride (di-NCA) monomers in reasonable yields with high purity. Five different di-NCAs were separately copolymerized with tert-butyl-l-glutamate NCA to obtain covalently crosslinked copolypeptides capable of forming hydrogels with varying crosslinker density. Comparison of hydrogel properties with residue structure revealed that different di-α-amino acids were not equivalent in crosslink formation. Notably, l-cystine was found to produce significantly weaker hydrogels compared to l-homocystine, l-cystathionine, and l-lanthionine, suggesting that l-cystine may be a sub-optimal choice of di-α-amino acid for preparation of copolypeptide networks. The di-α-amino acid crosslinkers also provided different chemical stability, where disulfide crosslinks were readily degraded by reduction, and thioether crosslinks were stable against reduction. This difference in response may provide a means to fine tune the reduction sensitivity of polypeptide biomaterial networks

The atmospheres of the hot-Jupiters Kepler-5b and Kepler-6b observed during occultations with Warm-Spitzer and Kepler

This paper reports the detection and the measurements of occultations of the two transiting hot giant exoplanets Kepler-5b and Kepler-6b by their parent stars. The observations are obtained in the near infrared with Spitzer Space Telescope and at optical wavelengths by combining more than a year of Kepler photometry. The investigation consists of constraining the eccentricities of these systems and of obtaining broad band emergent spectra for individual planets. For both targets, the occultations are detected at 3 sigma level at each wavelength with mid-occultation times consistent with circular orbits. The brightness temperatures of these planets are deduced from the infrared observations and reach T=1930+/-100K and T=1660+/-120K for Kepler-5b and Kepler-6b respectively. We measure optical geometric albedos A_g in the Kepler bandpass and find A_g=0.12+/-0.04 for Kepler-5b and A_g=0.11+/-0.04 for Kepler-6b leading to an upper limit for the Bond albedo of A_B < 0.17 in both cases. The observations for both planets are best described by models for which most of the incident energy is redistributed on the dayside, with only less than 10% of the absorbed stellar flux redistributed to the night side of these planets. The data for Kepler-5b favor a model without a temperature inversion, whereas for Kepler-6b they do not allow distinguishing between models with and without inversion.Comment: 26 pages, 18 figures, 3 tables, submitted to Ap