Protein-like Polymers Research Articles

Direct Characterization of Hydrophobic Hydration during Cold and Pressure Denaturation

Many computational approaches for large biomolecular systems renormalize the role of the solvent into the definition of effective inter-residue interactions by coarse-grained models to access biologically relevant time-scales. However, the discrete nature of water and its effects on protein stability, dynamics and function cannot be explored in a predictive way with models that implicitly describe the solvent. We present here, a new off-lattice coarse-grained protein-like polymer model combined with a coarse-grained water model to correctly capture the solvent contribution in determining the stability of the collapsed state and molecular interactions.

Folding of a single‐chain, information‐rich polypeptoid sequence into a highly ordered nanosheet

The design and synthesis of protein-like polymers is a fundamental challenge in materials science. A means to achieve this goal is to create synthetic polymers of defined sequence where all relevant folding information is incorporated into a single polymer strand. We present here the aqueous self-assembly of peptoid polymers (N-substituted glycines) into ultrathin, two-dimensional highly ordered nanosheets, where all folding information is encoded into a single chain. The sequence designs enforce a two-fold amphiphilic periodicity. Two sequences were considered: one with charged residues alternately positive and negative (alternating patterning), and one with charges segregated in positive and negative halves of the molecule (block patterning). Sheets form between pH 5 and 10 with the optimal conditions being pH 6 for the alternating sequence and pH 8 for the block sequence. Once assembled, the nanosheets remain stable between pH 6 and 10 with observed degradation beginning to occur below pH 6. The alternating charge nanosheets remain stable up to concentrations of 20% acetonitrile, whereas the block pattern displayed greater robustness remaining stable up to 30% acetonitrile. These observations are consistent with expectations based on considerations of the molecules' electrostatic interactions. This study represents an important step in the construction of abiotic materials founded on biological informatic and folding principles.

Free-floating ultrathin two-dimensional crystals from sequence-specific peptoid polymers

The design and synthesis of protein-like polymers is a fundamental challenge in materials science. A biomimetic approach is to explore the impact of monomer sequence on non-natural polymer structure and function. We present the aqueous self-assembly of two peptoid polymers into extremely thin two-dimensional (2D) crystalline sheets directed by periodic amphiphilicity, electrostatic recognition and aromatic interactions. Peptoids are sequence-specific, oligo-N-substituted glycine polymers designed to mimic the structure and functionality of proteins. Mixing a 1:1 ratio of two oppositely charged peptoid 36mers of a specific sequence in aqueous solution results in the formation of giant, free-floating sheets with only 2.7 nm thickness. Direct visualization of aligned individual peptoid chains in the sheet structure was achieved using aberration-corrected transmission electron microscopy. Specific binding of a protein to ligand-functionalized sheets was also demonstrated. The synthetic flexibility and biocompatibility of peptoids provide a flexible and robust platform for integrating functionality into defined 2D nanostructures.

Thermo-Induced Formation of Unimolecular and Multimolecular Micelles from Novel Double Hydrophilic Multiblock Copolymers of N,N-Dimethylacrylamide and N-Isopropylacrylamide

Two novel double hydrophilic multiblock copolymers of N,N-dimethylacrylamide and N-isopropylacrylamide, m-PDMAp-PNIPAMq, with varying degrees of polymerization (DPs) for PDMA and PNIPAM sequences (p and q) were synthesized via consecutive reversible addition-fragmentation chain transfer (RAFT) polymerizations using polytrithiocarbonate (1) as the chain transfer agent (Scheme 1), where PDMA is poly(N,N-dimethylacrylamide) and PNIPAM is poly(N-isopropylacrylamide). The DPs of PDMA and PNIPAM sequences were determined by 1H NMR, and the block numbers, i.e., number of PDMAp-PNIPAMq sequences (n), were obtained by comparing the molecular weights of multiblock copolymers to that of cleaved products as determined by gel permeation chromatography (GPC). m-PDMA42-PNIPAM37 and m-PDMA105-PNIPAM106 multiblock copolymers possess number-average molecular weights (Mn) of 4.62x10(4) and 9.53x10(4), respectively, and the polydispersities (Mw/Mn) are typically around 1.5. Block numbers of the obtained multiblock copolymers are ca. 4, which are considerably lower than the numbers of trithiocarbonate moieties per chain of 1 (approximately 20) and m-PDMAp precursors (approximately 6-7). PDMA homopolymer is water soluble to 100 degrees C, while PNIPAM has been well known to exhibit a lower critical solution temperature (LCST) at ca. 32 degrees C. In aqueous solution, m-PDMA42-PNIPAM37 and m-PDMA105-PNIPAM106 multiblock copolymers molecularly dissolve at room temperature, and their thermo-induced collapse and aggregation properties were characterized in detail by a combination of optical transmittance, fluorescence probe measurements, laser light scattering (LLS), and micro-differential scanning calorimetry (micro-DSC). It was found that chain lengths of PDMA and PNIPAM sequences exert dramatic effects on their aggregation behavior. m-PDMA105-PNIPAM106 multiblock copolymer behaves as protein-like polymers and exhibits intramolecular collapse upon heating, forming unimolecular flower-like micelles above the thermal phase transition temperature. On the other hand, m-PDMA42-PNIPAM37 multiblock copolymer exhibits collapse and intermolecular aggregation, forming associated multimolecular micelles at elevated temperatures. The intriguing aggregation behavior of this novel type of double hydrophilic multiblock copolymers argues well for their potential applications in many fields such as biomaterials and biomedicines.

Crosslinked hyaluronan with a protein‐like polymer: Novel bioresorbable films for biomedical applications

In this work, novel hydrogel films based on hyaluronan (HA) chemically crosslinked with the alpha,beta-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-D,L-aspartamide (PHEA-EDA) were produced by solution casting method. The goal was to exploit both the biological key role of HA in tissue repair and regeneration, and the versatility of a synthetic protein-like polymer as the PHEA-EDA, in order to obtain biomaterials with physicochemical and biological properties suitable for a clinical use. By varying the molar ratio between the PHEA-EDA amino groups and HA carboxyl groups, three different films were obtained and characterized. Particularly FTIR, swelling, hydrolysis, and enzymatic degradation studies were performed. In addition, the cytocompatibility of HA/PHEA-EDA hydrogel films was evaluated using human derm fibroblasts, by means of MTT and trypan blue exclusion assays. The high swelling capability, the long-term hydrolysis resistance, and the resistance to hyaluronidase greater than that of only HA, together with the cell compatibility, have suggested the potential application of these novel HA-based hydrogel films in the biomedical field of tissue engineering.

Novel cationic polyaspartamide with covalently linked carboxypropyl-trimethyl ammonium chloride as a candidate vector for gene delivery

The non-viral gene vector properties of a protein-like polymer, the α,β-poly( N-2-hydroxyethyl)- d, l-aspartamide (PHEA) were investigated after its derivatization with 3-(carboxypropyl)trimethyl-ammonium chloride (CPTA) as molecule bearing cationic groups, in order to obtain stable polycations able to condense DNA. PHEA was firstly functionalized with hydrazide pendant groups by reaction with hydrazine monohydrate (HYD), obtaining the polyhydrazide α,β-poly( N-2-hydroxyethyl/carbazate)- d, l-aspartamide (PHEA–HYD). In this paper we reported that polymer functionalization degree can be easily modulated by varying reaction conditions, so allowing us to produce two PHEA derivatives at different molar percentage of hydrazide groups. Subsequently, condensation reaction of PHEA–HYD copolymers with CPTA yielded α,β-poly( N-2-hydroxyethyl)- N-carbazate[ N′-(3-trimethylammonium chloride)propylhydrazide]- d, l-aspartamide (PHEA–HYD–CPTA) polycation derivatives. In vitro studies were carried out to evaluate polycations ability to complex DNA and to protect it from nuclease degradation. Obtained results demonstrated the good efficiency of our new PHEA-polycations derivatives, PHEA–HYD–CPTA, to complex and condense genomic material even at very low polycation/DNA weight ratio.

Synthesis and characterization of polyaminoacidic polycations for gene delivery

The properties as non viral gene vector of a protein-like polymer, the α, β-poly( N-2-hydroxyethyl)- d, l-aspartamide (PHEA) were exploited after its derivatization with 3-(carboxypropyl)trimethyl-ammonium chloride (CPTA) as molecule bearing a cationic group, in order to obtain stable polycations able to condense DNA. PHEA was firstly functionalized with aminic pendant groups by reaction with ethylenediamine (EDA) obtaining the α, β-poly( N-2-hydroxyethyl)(2-aminoethylcarbamate)- d, l-aspartamide (PHEA-EDA) copolymer. We demonstrated that polymer functionalization degree is easily modulable by varying reaction conditions, so allowing to produce two PHEA-EDA derivatives at different molar percentage of amine groups. Subsequently, the condensation reaction of PHEA-EDA copolymers with CPTA yielded α, β-poly( N-2-hydroxyethyl)(2-[3-(trimethylammonium chloride)propylamide]-amidoethylcarbamate)- d, l-aspartamide (PHEA-EDA-CPTA) polycation derivatives. In vitro studies were carried out to evaluate polycations ability to complex DNA and to protect it from nuclease degradation. Obtained results demonstrated the good ability of our new PHEA polycationic derivatives, PHEA-EDA-CPTA, to complex and condense genomic material, neutralizing its anionic charge even at very low polycation/DNA weight ratio. Finally, PHEA-EDA-CPTA polycations were characterized by in vitro cytotoxicity studies to evaluate their effects on the viability of HuH-6 human hepatocellular carcinoma cells by MTS assay. No cytotoxicity was evidenced by both polycationic derivatives after 48 h of incubation at all tested concentrations.

Stabilization of surface-immobilized enzymes using grafted polymers

We introduce a two-dimensional lattice model of immobilization and stabilization of proteinlike polymers using grafted polymers. The protein is designed to have a specific bulk conformation reproducing a catalytic cleft of natural enzymes. Our model predicts a first order denaturing adsorption transition of free proteins. On the other hand, for an immobilized protein we observe a more gradual disappearance of the hydrophobic centers accompanied by adsorption. We show that, using hydrophilic grafted polymers of proper length and grafting density, the conformation as well as the hydrophobic centers of the protein can be restored.

Conformational properties and elastic behavior of protein-like lattice polymers

The interior conformations and elastic behaviors of protein-like lattice polymers in the process of tensile elongation are investigated by means of Monte Carlo method and the (310) hybrid lattice model. Here (HHPPHPP) x sequence of protein-like polymer chains is adopted. It is found that three types of contacts, i.e. HH-, PP- and HP-contact, have different behavior in the process of elongation. Second structures of protein-like chains, i.e. helical, coil and expanded structures, have distinct characteristic in our simulation. The average energy, the Helmholtz free energy and elastic force are also investigated at different temperature. Moreover, 〈 s f i * 〉 and 〈 δ *〉 as a function of elongation ratio carefully reflect the shape change in the process of tensile elongation, and the snapshots of contact maps can directly explain the interior conformation change of protein-like chains, therefore, here we give some discussions about the shape and the snapshots of contact maps. These investigations may provide some insights into the elastic behavior of protein-like chains.

Collapse transitions in protein-like lattice polymers: The effect of sequence patterns

The collapse transition of lattice protein-like heteropolymers has been studied by means of the Monte Carlo method. The protein model has been reduced to the α-carbon trace restricted to a high coordination lattice. The sequences of model heteropolymers contain two types of mers: hydrophobic/nonpolar (H) and hydrophilic/polar (P). Interactions of HH and PP pairs were assumed to be negative (weaker attractions of PP pairs) while the contact energy for HP pairs was equal to zero. All sequence-specific short-range interactions have been neglected in the present studies. It has been found that homopolymeric chains undergo a smooth collapse transition to a dense globular state. The globule lacks any signatures of local ordering that could be interpreted as a model of protein secondary structure. Hetero-polymers with the sequences of hydrophilic and hydrophobic residues characteristic for α- and β-type proteins undergo a somewhat sharper (though continuous) collapse transition to a dense globular state with elements of local ordering controlled by the sequence. The helical pattern induces more secondary structure than the β-type pattern. For all examined sequences the level of local ordering was lower than the average secondary structure content of globular proteins. The results are compared with other theoretical work and with known experimental facts. The implications for the reduced modeling of protein systems are briefly discussed. © 1997 John Wiley & Sons, Inc. Biopoly 42: 537–548, 1997

Photoinduced Electron Transfer for an Eosin-Tyrosine Conjugate. Activity of the Tyrosinate Anion in Long Range Electron Transfer in a Protein-like Polymer Matrix

ADVERTISEMENT RETURN TO ISSUEArticleNEXTPhotoinduced Electron Transfer for an Eosin-Tyrosine Conjugate. Activity of the Tyrosinate Anion in Long Range Electron Transfer in a Protein-like Polymer MatrixGuilford Jones II, Zhiming Feng, and Churl OhCite this: J. Phys. Chem. 1995, 99, 12, 3883–3888Publication Date (Print):March 1, 1995Publication History Published online1 May 2002Published inissue 1 March 1995https://doi.org/10.1021/j100012a001RIGHTS & PERMISSIONSArticle Views156Altmetric-Citations6LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (1 MB) Get e-Alerts

Oral immunization of rats with proteinoid microspheres encapsulating influenza virus antigens.

Influenza virus antigen microspheres were prepared by a pH-dependent process using a protein-like polymer (proteinoid) made by thermal condensation of amino acids. The efficacy of these preparations to induce specific IgG responses when used as oral vaccines in rats was evaluated. A single enteric dose of M1 entrapped in proteinoid microspheres was able to induce a significant IgG response to M1 as early as 2 weeks postdosing, while rats dosed orally with the same M1 total dose (no microspheres) showed no detectable antibody response. An unencapsulated hemagglutinin and neuraminidase (HA-NA) preparation induced a moderate anti HA-NA IgG response. A single enteric dose of HA-NA spheres induced a response in 33% of the rats; this response was up to eight times higher than that observed in the rats dosed with unencapsulated antigen.

The specificity of proanthocyanidin-protein interactions.

The proanthocyanidins or condensed tannins, phenolic polymers which are synthesized by many plants, characteristically bind and precipitate proteins. The specificity of the interaction was investigated using a competitive binding assay to compare directly the affinities of various proteins and synthetic polymers for the tannin obtained from Sorghum bicolor (Lin.) Moench. At pH 4.9, the relative affinities range over more than 4 orders of magnitude, indicating that this proanthocyanidin interacts quite selectively with protein and protein-like polymers. The affinity for tannins is an inverse function of the size of the polymer, and peptides with less than six residues interact very weakly with tannin. Proteins are precipitated by proanthocyanidins most efficiently at pH values near their isoelectric points. Proline-rich proteins and polymers have very high affinities for tannin. Tightly coiled globular proteins have much lower affinities for tannin than conformationally loose proteins.

Polyamino Acids: Preparation from Reported Proportions of "Prebiotic" and Extraterrestrial Amino Acids

Polyamino acids were thermally prepared from the proportions of amino acids identified (sometimes after hydrolysis) among the products of simulated prebiotic syntheses and (after hydrolysis) in lunar and meteoritic samples. Inferences are made concerning the composition of prebiotic protein and the possible extraterrestrial existence of protein-like polymers.

STUDIES ON THE MECHANISM OF IODINE UPTAKE BY THYROID TISSUE

To investigate each process of iodine uptake by thyroid tissue, experiments were performed under various conditions. Results obtained were as follows : 1) Accelerative effects of various inorganic salts, and inhibitory effects of sodium cyanide methylthiouracil and various plant components were observed in I131 uptake experiments with frozen thyroid tissue. 2) Inhibitory effect of methylthiouracil on the process of I131 binding by thyroid was observed. Its binding force became so weak that the bound form of I131 in thyroid slices was transformed into the liberated form by action of potassium rodanate, 3) The existence of coupling process of I131 to tyrosine molecules, loosely bound by some protein-like polymer in thyroid tissue was proved. Hypothesis of “bound tyrosine” was proved by using C14 tyrosine incorporation method. Inhibitory effects of sodium cyanide and methylthiouracil on the process of coupling I131 to “bound tyrosine” were observed. 4) I131 uptake by thyroid slices was more sensitively inhibited than their oxygen consumption under various conditions, such as replacement of incubation medium, addition of sodium cyanide, methylthiouracil, various plant components, and potassium iodide.