Backbone Bonds Research Articles

Global Genome Mining Reveals the Distribution of Diverse Thioamidated RiPP Biosynthesis Gene Clusters

Thioamidated ribosomally synthesized and post-translationally modified peptides (RiPPs) are recently characterized natural products with wide range of potent bioactivities, such as antibiotic, antiproliferative, and cytotoxic activities. These peptides are distinguished by the presence of thioamide bonds in the peptide backbone catalyzed by the YcaO-TfuA protein pair with its genes adjacent to each other. Genome mining has facilitated an in silico approach to identify biosynthesis gene clusters (BGCs) responsible for thioamidated RiPP production. In this work, publicly available genomic data was used to detect and illustrate the diversity of putative BGCs encoding for thioamidated RiPPs. AntiSMASH and RiPPER analysis identified 613 unique TfuA-related gene cluster families (GCFs) and 797 precursor peptide families, even on phyla where the presence of these clusters have not been previously described. Several additional biosynthesis genes are colocalized with the detected BGCs, suggesting an array of possible chemical modifications. This study shows that thioamidated RiPPs occupy a widely unexplored chemical landscape.

Iso-anchorene is an endogenous metabolite that inhibits primary root growth in Arabidopsis.

Carotenoid-derived regulatory metabolites and hormones are generally known to arise through the oxidative cleavage of a single double bond in the carotenoid backbone, which yields mono-carbonyl products called apocarotenoids. However, the extended conjugated double bond system of these pigments predestines them also to repeated cleavage forming dialdehyde products, diapocarotenoids, which have been less investigated due to their instability and low abundance. Recently, we reported on the short diapocarotenoid anchorene as an endogenous Arabidopsis metabolite and specific signaling molecule that promotes anchor root formation. In this work, we investigated the biological activity of a synthetic isomer of anchorene, iso-anchorene, which can be derived from repeated carotenoid cleavage. We show that iso-anchorene is a growth inhibitor that specifically inhibits primary root growth by reducing cell division rates in the root apical meristem. Using auxin efflux transporter marker lines, we also show that the effect of iso-anchorene on primary root growth involves the modulation of auxin homeostasis. Moreover, by using liquid chromatography-mass spectrometry analysis, we demonstrate that iso-anchorene is a natural Arabidopsis metabolite. Chemical inhibition of carotenoid biosynthesis led to a significant decrease in the iso-anchorene level, indicating that it originates from this metabolic pathway. Taken together, our results reveal a novel carotenoid-derived regulatory metabolite with a specific biological function that affects root growth, manifesting the biological importance of diapocarotenoids.

Stitching together a nm thick peptide-based semiconductor sheet using UV light

Langmuir monolayer allows for a two-dimensional nano-scale organization of amphiphilic molecules. We have adapted this technique to measure lateral and transverse conductivity in confined peptide nanosheets for the first time. We reported that two retro-isomers amphipathic peptides form stable monolayers showing a semiconductor-like behavior. Both peptides exhibit the same hydrophobicity and surface stability. They differ in the lateral conductivity and current-voltage due to the asymmetric peptide bond backbone orientation at the interface. Both peptides contain several tyrosines allowing the lateral crosslinking in neighboring molecules induced by UVB. UVB-light induces changes in the lateral conductivity and current-voltage behavior as well as monolayer heterogeneity monitored by Brewster Angle Microscopy. The semiconductor properties depend on the peptide bond backbone orientation and tyrosine crosslinking. Our results indicate that one may design extended nano-sheets with particular electric properties, reminiscent of semiconductors. We propose to exploit such properties for biosensing and neural interfaces.

Molecular Dynamics Simulations of Self-Healing Topological Copolymers with a Comblike Structure

Topological copolymers with a comblike structure have been found to have the ability to recover without the need for extraneous material components and the use of external stimuli; however, a systematic and fundamental understanding at the molecular level is still lacking. In this work, coarse-grained molecular dynamics (CGMD) simulation and noncovalent interaction (NCI) analysis were employed to investigate a model system of self-healing comblike copolymers consisting of methyl methacrylate (MMA) and n-butyl acrylate (n-BA). Specifically, the different interactions of neighboring macromolecules were analyzed by NCI. Then, the influence of the following three parameters on the mechanical properties and interpenetration of side chains was probed: (1) a spacer between side chains lg, (2) average molecular weight per backbone bond mb, and (3) the flexibility of side chains kₛ. Based on the optimum of the three parameters, self-healing simulations were performed to examine the mechanical behavior of the system at different healing temperatures and healing times. The NCI results reveal that the sectional backbone chains are forced to stretch due to the steric repulsion and the side chains of neighboring molecules are interpenetrated due to the attraction of van der Waals force. Favorable steric repulsion and a spacer between side chains allow for interpenetration of side chains of neighboring macromolecules, leading to optimal mechanical properties with the graft polymer composition φ = lg/(lg + Rₛc) ≅ 3/7, where Rₛc and lg are the length of side chains and the spacer separating two consecutive side chains along the polymer backbone, respectively. Interpenetration of side chains is negatively correlated with the average molecular weight per backbone bond (mb) for graft chains. Comblike copolymers with stiff side chains tend to form lock-and-key structures, which are conducive to closer interpenetration and better mechanical properties.

A Crystalline Three-Dimensional Covalent Organic Framework with Flexible Building Blocks.

The construction of three-dimensional covalent organic frameworks (3D COFs) has proven to be very challenging, as their synthetic driving force mainly comes from the formation of covalent bonds. To facilitate the synthesis, rigid building blocks are always the first choice for designing 3D COFs. In principle, it should be very appealing to construct 3D COFs from flexible building blocks, but there are some obstacles blocking the development of such systems, especially for the designed synthesis and structure determination. Herein, we reported a novel highly crystalline 3D COF (FCOF-5) with flexible C-O single bonds in the building block backbone. By merging 17 continuous rotation electron diffraction data sets, we successfully determined the crystal structure of FCOF-5 to be a 6-fold interpenetrated pts topology. Interestingly, FCOF-5 is flexible and can undergo reversible expansion/contraction upon vapor adsorption/desorption, indicating a breathing motion. Moreover, a smart soft polymer composite film with FCOF-5 was fabricated, which can show a reversible vapor-triggered shape transformation. Therefore, 3D COFs constructed from flexible building blocks can exhibit interesting breathing behavior, and finally, a totally new type of soft porous crystals made of pure organic framework was announced.

Unraveling the Molecular Mechanisms That Influence the Color and Stability of Four Lutein Crystal Forms

Lutein belongs to the carotenoid compound family, which is a special group of hydrocarbon pigments characterized by π-conjugated double bonds in the molecular backbone. Four lutein crystal forms wi...

Hypervariability of accessible and inaccessible conformational space of proteins.

Proteins undergo motions in a range of amplitudes, from domain motions to backbone rotations, leading to changes in (φ,ψ) torsion angles and small-scale bond vibrations and angle bending. Here, we study the extent of variations in (φ,ψ) values in proteins and the effects of bond geometry variations due to vibrational motions in a protein on the accessible, (steric clash-free) (φ,ψ) space. We perform 1-fs timestep unconstrained molecular dynamics simulations on super-high-resolution protein structures. Extent of variations in bond geometry during the simulation is within acceptable ranges of bond lengths and angles. However, the steric clash-free (φ,ψ) space continuously changes as seen in bond geometry-specific (φ,ψ) steric maps at the residue level during simulations. (φ,ψ) regions that have steric clash at one timepoint can become steric clash-free at a different timepoint through minor adjustments to backbone bond lengths and angles. Also instances of (φ,ψ) transitions from the left to right half of the (φ,ψ) map in consecutive snapshots of the trajectory are seen. Although the two quadrants are separated by a steric clash-prone region, corresponding to a high-energy barrier, height of this barrier is lowered by adjusting the bond geometry such that a bridging region of steric clash-free, low-energy (φ,ψ) values is formed. We demonstrate the idea of dynamically varying nature of acceptable and accessible (φ,ψ) steric space in proteins, which has implications for protein folding; proteins could sample (φ,ψ) space which is originally considered to be inaccessible, during folding, through minor adjustments to their backbone bond geometry.

Molecular Packing Interaction in DNA Crystals

DNA crystallography provides essential structural information to understand the biochemical and biological functions of oligonucleotides. Therefore, it is necessary to understand the factors affecting crystallization of DNA to develop a strategy for production of diffraction-quality DNA crystals. We analyzed key factors affecting intermolecular interactions in 509 DNA crystals from the Nucleic Acid Database and Protein Databank. Packing interactions in DNA crystals were classified into four categories based on the intermolecular hydrogen bonds in base or backbone, and their correlations with other factors were analyzed. From this analysis, we confirmed that hydrogen bonding between terminal end and mid-region is most common in crystal packing and in high-resolution crystal structures. Interestingly, P212121 is highly preferred in DNA crystals in general, but the P61 space group is relatively abundant in A-DNA crystals. Accordingly, P212121 contains more terminal end-mid-region interactions than other space groups, confirming the significance of this interaction. While metals play a role in the production of a good crystal in B-DNA conformation, their effect is not significant in other conformations. From these analyses, we found that packing interaction and other factors have a strong influence on the quality of DNA crystals and provide key information to predict crystal growth of candidate oligonucleotides.

(Invited) Development of Versatile Polymer Materials for Anion Exchange Membranes in Electrochemical Energy Conversion Technology

Anion exchange membranes (AEMs) based on hydroxide-conducting polymers are a key component for anion-based electrochemical energy technology such as fuel cells, electrolyzers, and advanced batteries. Although these alkaline electrochemical applications offer a promising alternative to acidic proton exchange membrane electrochemical devices, access to alkaline-stable and high-performing polymer electrolyte materials has remained elusive until now. Despite vigorous research of AEM polymer design, examples of high-performance polymers with good alkaline stability at an elevated temperature are uncommon. Traditional aromatic polymers used in AEM applications contain a heteroatomic backbone linkage which is prone to degradation via nucleophilic attack by hydroxide ion.In this presentation, I will highlight recent progress at the Bae group of Rensselaer Polytechnic Institute in the development of advanced hydroxide-conducting polymers and technology transfer effort to commercialize materials for AEM applications. We have developed new synthetic methods that produce polymer design made of all C−C bond backbone and a flexible chain-tethered quaternary ammonium group and that provide an effective solution to the problem of alkaline stability. The advantage of good solvent processability, synthetic versatility, and convenient scalability of the reaction process has generated considerable interest of these polymers, and they are considered leading candidates for commercial standard AEM. AEM fuel cells, electrolyzer, and vanadium redox flow battery tests of some of the developed polymer membranes showed excellent performance, suggesting that this new class of AEMs open a new avenue to electrochemical devices with real-world applications.

The Effect of Backbone Structure on Functional Properties in Anion Exchange Membranes; Comparison of Poly(fluorene) with Poly(biphenylene) and Poly(terphenylene)s

The irreversible environmental impacts caused by energy generation from fossil fuels calls for a paradigm shift in the energy conversion and storage. Among many alternative energy technologies hydrogen based electrochemical devices gain significance because of its high efficiency and environmentally benign byproduct formation. Ion exchange polymers play a key role in electrochemical devices as solid-state electrolytes conducting ions between the electrodes while acting as a physical barrier to reactants and electrons. Electrochemical reactions carried out under high pH medium in fuel cells and electrolyzers using anion exchange membranes (AEMs) have gained significant traction recently, due to the prospect of using non-platinum group metal electrocatalyst for the redox reactions. While AEMs remain a crucial part of electrochemical devices such as alkaline exchange membrane fuel cells and alkaline electrolyzers, the absence of a suitable membrane is an impediment for the widespread usage of these technologies. Recently our group synthesized several anion exchange polymers via super acid catalyzed Friedel-Crafts polycondensation. These AEMs, BPN1-100, m-TPN1-100 and p-TPN1-100 showed excellent stability in alkaline medium due to the absence of labile aryl-ether bonds in the polymer backbone. Additionally, they also exhibit good ionic conductivities and mechanical properties. In order to further understand the effects of polymer backbone morphology in AEM properties another polymer FMN1-100 was synthesized. In this study, properties of the AEMs BPN1-100, m-TPN1-100, p-TPN1-100, and FMN1-100 (Figure 1) were evaluated and compared for the purpose of anion exchange polymer electrolytes. Furthermore, FMN2-60 and FMN2-50 containing dication side chains were synthesized and compared against FMN1-100 containing a monocation side chain. The effect of the backbone architecture and side chain cations on the AEM properties such as, ionic conductivity, water uptake ratio, mechanical properties, morphology, and alkaline stability were investigated to broaden the knowledge of polymer design for AEMs. Figure 1

Comparison of Novel 1,1-Diphenylethylene Alternating Copolymer and Polystyrene Based Anion Exchange Membranes

This research investigates 1,1-diphenylethylene as a monomer in polymeric ion exchange membranes through the synthesis of a novel alternating copolymer functionalized for ion transport and analysis of mechanical and conductive properties. This will further the development of cost effective and high-performance ion exchange membranes, enabling energy systems that employ ion-transporting membranes, like fuel cells and electrolyzers, to become more economically viable, which in turn would lead to cleaner and more sustainable energy production.The goal of the project is to develop an understanding of chemical structure-physical property relationships to make self-assembling ion-conducting channels in ionomers which have physical properties that prevent the excess swelling that leads to the mechanical failure of membranes. In this vein, anion exchange membranes (AEMs) based on 1,1-diphenylethylene were synthesized and their ion conducting properties and physical state were characterized. Poly(1,1-diphenylethylene-alt-butadiene) alternating copolymer was synthesized via anionic polymerization, then selectively hydrogenated to eliminate double bonds in the polymer backbone. The pendant aromatic rings of the selectively hydrogenated poly(1,1-diphenylethylene-alt-butadiene) were then subjected to quantitatively controlled functionalized by super acid catalyzed Friedel-Crafts bromoalkylation, then aminated with trimethylamine. AEMs spanning a wide range of ion exchange capacities (IECs), 0.39-1.99 milliequiv./gram (meq./g), were made. Conductivity increased with IEC and temperature. Polystyrene based AEMs of similar IECs, 0.38-2.14 meq/g, were synthesized as a standard to compare the 1,1-diphenylethylene based copolymers. The 1,1-diphenylethylene based copolymers had favorable conductivities compared to polystyrene membranes of similar IEC. The glass transition temperature, water uptake, and dimensional swelling were investigated to explain the difference in conductivities between the two species. Figure 1

Chain flexibility and glass transition temperatures of poly(n-alkyl (meth)acrylate)s: Implications of tacticity and chain dynamics

The relationship between chain microstructure and glass transition temperature (Tg) is complicated for poly(alkyl methacrylate)s and poly(alkyl acrylate)s. Despite intensive studies, relationships between the structures of these polymers and their properties, including solution characteristics and Tg, are still controversial. Solution properties, chain conformations, including Flory's characteristic ratio (C∞), persistence length (lp), and chain diameters, and Tg are reported for series of poly(n-alkyl acrylate)s and poly(n-alkyl methacrylate)s having alkyl side chain lengths (n) ranging from 1 to 10 carbons in length, with uniform and well-characterized tacticities. Chain flexibilities of both series of polymers decrease as n increases, reflecting increased hindrances to rotation about backbone bonds as side chains become longer. Conversely, the Tgs for both series of polymers decrease substantially as n increases, reflecting the greater side chain mobilities of long alkyl substituents. For shorter alkyl chain lengths, Tgs for the poly(n-alkyl acrylate)s are much lower than for the corresponding poly(n-alkyl methacrylate)s, a difference which has been attributed in the past to the presumed reduced chain flexibility of polymethacrylates due to the presence of the α-methyl substituent. However, contrary to such expectations, C∞ and lp values for these two series of polymers are nearly identical at a given n value, except for the longest n-alkyl substituents. Instead, the differences in Tg may be attributed to the differences in tacticity of the two series – almost ideally atactic for the poly(n-alkyl acrylate)s but high in syndiotacticity for the poly(n-alkyl methacrylate)s. The Tgs for the two series of polymers approach that of polyethylene at longer alkyl chain lengths. In addition, the effects of tacticity and chain dynamics on C∞, lp, and Tg of poly(methyl methacrylate) is discussed.

Improving Storage Stability and Physicochemical Performance of Styrene-Butadiene-Styrene Asphalt Binder Modified with Nanosilica

Due to storage stability drawbacks of polymer-modified bitumen (PMB), this study investigated the storage stability and physicochemical performance of Styrene-Butadiene-Styrene (SBS) asphalt binders (herein PMB) modified with Silicone surface-treated nanosilica (SNS). Dosages 0% (control), 1.5%, 3% and 5% SNS powder were added to PMB to prepare modified binders. Hot storage, Viscosity, Multiple Stress Creep Recovery (MSCR), Scanning Electron Microscopy (SEM), Fluorescence Microscopy (FM), Linear Amplitude Sweep (LAS), Fourier Transform Infrared (FTIR), and Proton Nuclear Magnetic Resonance (1H-NMR) tests were conducted using modified binders. The study found that adding nanosilica powder to PMB improved storage stability, increased viscosity and complex modulus, and reduced rutting of binders. However, this bitumen modification was not beneficial to fatigue cracking. The performance improvement was because of the interaction between the polymer and nanosilica, creating a new polymer-nanosilica network which lowered the dynamics around the SNS particles, thereby reducing phase separation. Further, the Silicone Si–O–Si backbone bond present in SNS modified asphalt binder reduced temperature sensitivity thereby preventing thermal degradation at high storage temperature. Nanosilica modified binders presented well-dispersed nanosilica particles in the asphalt matrix. The modification mechanism was predominantly physical. Overall, the study concluded that nanosilica improves storage stability, rutting, and morphology of PMB binders.

Characterization of Insulin Dimers by Top-Down Mass Spectrometry.

High-molecular weight products (HMWP) are an important critical quality attribute in research and development of insulin biopharmaceuticals. We here demonstrate on two case studies of covalent insulin dimers, induced by Fe2+ incubation or ultraviolet (UV) light stress, that de novo characterization in top-down mass spectrometry (MS) workflows can identify cross-link types and sites. On the MS2 level, electron-transfer/higher-energy collision dissociation (EThcD) efficiently cleaved the interchain disulfide bonds in the dimers to reveal cross-link connectivities between chains. The combined utilization of EThcD and 213 nm ultraviolet photodissociation (UVPD) facilitated identification of the chemical composition of the cross-links. Identification of cross-link sites between chains at residue level was achievable for both dimers with MS3 analysis of MS2 fragments cleaved at the cross-link or additionally the interchain disulfide bonds. UVPD provided identification of cross-link sites in the Fe2+-induced dimer without MS3, while cross-link site identification with MS2 was not possible for the UV light-induced dimer. Thus, using varied multistage approaches, it was discovered that in the UV light-induced dimer, Tyr14 of the A-chain participated in an -O-S- cross-link in which the sulfur was derived either from Cys7 or Cys19 of the B-chain. In the Fe2+-induced dimer, Phe1 from both B-chains were cross-linked through a -CH2-. The UV chromophoric side chain of Phe1 was indicated in the cross-link, explaining why UVPD-MS2 was effective in fragmenting the cross-link and nearby backbone bonds. Our results demonstrated that higher-energy collisional dissociation (HCD), EThcD, and UVPD combined with MS3 were powerful tools for direct de novo characterization of cross-linked insulin dimers.

Combinatorial synthesis of redox-responsive cationic polypeptoids for intracellular protein delivery application

Biologics play an essential role in treating various indications from cancers to the metabolic diseases, while the current development of new classes of intracellular-acting protein drugs is still hindered because of high molecular mass and overall hydrophilicity of proteins creating extremely poor permeability across cell membrane. Hence, there remains an unmet need to develop safe, potent approaches to augment intracellular protein delivery efficiency. Here, we described a facile multi-component reaction system for generating a small library of redox-responsive cationic polypeptoids with high bio-compatibility. The co-assembly of optimized polymer with protein leads to the formation of compacted nanocomplexes with smaller size and high encapsulation efficiency, thus improving cellular internalization via the macropinocytosis and/or caveolae-mediated endocytosis mainly. After endo-lysosomal escape, the nanocomplexes can be disassociated to efficiently release cargo proteins into the cytosol, owing to the intracellular glutathione (GSH)-triggered rapid cleavage of disulfide bonds in polymers backbone. As a result, we screened a promising platform reagent for efficient cytosolic protein delivery application.

Abstract 1234: The anticancer drug ABTL0812 induces cancer cell death by impairing Akt/mTORC1 axis and inducing ER stress-mediated cytotoxic autophagy

Abstract ABTL0812 is a first-in-class small molecule with anticancer activity currently in Phase 2a clinical evaluation in patients with advanced endometrial and squamous NSCLC. We have previously described that ABTL0812 induces TRIB3 pseudokinase expression, resulting in inhibition of the Akt-mTORC1 axis and autophagy-mediated cancer cell death. However, classical PI3K/Akt/mTOR inhibitors do not induce an autophagy as strong as ABTL0812 does, therefore we aimed to further elucidate the molecular mechanism responsible for the cytotoxic autophagy which causes ABTL0812 anticancer activity. ABTL0812 induced UPR hallmarks ATF4, CHOP and TRIB3 in vitro in lung, endometrial and pancreatic cancer cell lines, as well as in non-tumor cells. Nevertheless, therapeutic concentrations of ABTL0812 did not induce cytotoxic autophagy in non-tumor cells. Furthermore, genetic or pharmacological inhibition of the UPR resulted in impaired ABTL0812 cytotoxicity in cancer cells. Expression of UPR markers (ATF4, CHOP and TRIB3) in response to ABTL0812 treatment were also validated in xenograft models. In order to uncover the precise molecular mechanism involved in ABTL0812-induced UPR and cytotoxic autophagy we undertook a comprehensive sphingolipidomic analysis, since changes in sphingolipids have been reported to contribute to activation of both UPR and autophagy. ABTL0812 treatment resulted in increased levels of long chain dihydroceramides in cultured cancer cells as well as in vivo. Mechanistically, ABTL0812 impaired desaturase-1 activity (Des-1), the enzyme that introduces a 4,5-trans-double bond in the sphingolipid backbone of dihydroceramides to generate ceramides. Accordingly, in vitro incubation of cancer cells with dihydroceramides resulted in activation of UPR, autophagy and cytotoxicity. Of interest, we observed that tumor cells showed higher Des-1 expression levels than non-tumor cells. Finally, we showed that Des-1 inhibition (GT11) and mTORC1 inhibition (everolimus) collaborate to promote autophagy and cancer cell death, simulating ABTL0812 activity. Furthermore, we have validated the increased expression of CHOP and TRIB3 mRNA levels in blood samples from ABTL0812 treated patients. These biomarkers are currently used as pharmacodynamic biomarkers in the ongoing phase 2 clinical trial in patients with squamous NSCLC and endometrial cancer. To our knowledge, this is the first time that UPR markers are reported to change in human blood in response to any drug treatment. In conclusion, we have shown that ABTL0812 triggers a sustained ER stress and UPR activation mediated by the impairment of Des-1 activity which collaborates with mTORC1 inhibition to induce cytotoxic autophagy in cancer cells, which offers improved anticancer activity over just inhibiting mTORC1. Citation Format: Pau Muñoz-Guardiola, Josefina Casas, Elisabet Megías-Roda, Hector Perez-Montoyo, Sonia Solé-Sánchez, Marc Yeste-Velasco, Tatiana Erazo, Nora Diéguez-Martínez, Sergio Espinosa-Gil, Guillermo Yoldi, Cristina Muñoz-Pinedo, Miguel F. Segura, Jose Alfon, Gemma Fabriàs, Guillermo Velasco, Carles Domenech, Jose M. Lizcano. The anticancer drug ABTL0812 induces cancer cell death by impairing Akt/mTORC1 axis and inducing ER stress-mediated cytotoxic autophagy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1234.

1,4-Disubstituted 1,2,3-Triazoles as Amide Bond Surrogates for the Stabilisation of Linear Peptides with Biological Activity.

Peptides represent an important class of biologically active molecules with high potential for the development of diagnostic and therapeutic agents due to their structural diversity, favourable pharmacokinetic properties, and synthetic availability. However, the widespread use of peptides and conjugates thereof in clinical applications can be hampered by their low stability in vivo due to rapid degradation by endogenous proteases. A promising approach to circumvent this potential limitation includes the substitution of metabolically labile amide bonds in the peptide backbone by stable isosteric amide bond mimetics. In this review, we focus on the incorporation of 1,4-disubstituted 1,2,3-triazoles as amide bond surrogates in linear peptides with the aim to increase their stability without impacting their biological function(s). We highlight the properties of this heterocycle as a trans-amide bond surrogate and summarise approaches for the synthesis of triazole-containing peptidomimetics via the Cu(I)-catalysed azide-alkyne cycloaddition (CuAAC). The impacts of the incorporation of triazoles in the backbone of diverse peptides on their biological properties such as, e.g., blood serum stability and affinity as well as selectivity towards their respective molecular target(s) are discussed.

Improvement in the transience and mechanical performance of flexible Poly(phthalaldehyde) substrates

Cyclic poly(phthalaldehyde) (PPHA) is a metastable polymer that depolymerizes to ortho-phthalaldehyde (o-PHA) at ambient temperatures. Both high molecular weights and a long shelf-life can be achieved. After an external stimulus trigger has been activated to break polymer backbone bonds, PPHA undergoes rapid depolymerization from the solid state. Flexible PPHA substrates can be made by mixing the polymer with traditional non-volatile plasticizers, however the solubility of plasticizers in PPHA is sometimes poor, and any solid products left behind after depolymerization can hinder the transience of the mixture. Hansen solubility parameters for PPHA were obtained and used to predict the solubility of plasticizers in PPHA. The freezing point of the degraded remnants is proportional to the total mole fraction of additives present in any given PPHA formulation. The colligative properties of o-PHA were obtained and used to estimate the freezing point depression of the transient remnants for multi-component mixtures. A single additive approach to plasticizing PPHA is presented in this study using diethyl adipate (DEA). Mechanical properties of PPHA films containing DEA were characterized. Glass transition temperature (Tg) values between 99.5 °C and 12.5 °C can be achieved using THF solvent to cast the PPHA-DEA film. A Tg of 187 °C was extrapolated for pure PPHA with no residual solvent. The flexibility of the DEA loaded PPHA films greatly improved at high DEA loadings. DEA also improved the transient depolymerization performance of DEA loaded PPHA resulting in complete liquification after depolymerization.

ABA triblock copolyesters composed of poly(l-lactide) A hard blocks: comparison of amorphous and crystalline unsaturated aliphatic polyesters as B soft blocks

The property profiles of ABA triblock copolymers can be precisely customized by changing the chemical structure of the components. The identification of the midblock is the key point in the development of PLLA-containing ABA triblock copolymers. Two kinds of unsaturated aliphatic polyesters, crystalline poly(cis-butene succinate) (PcBS) and amorphous poly(cis-butene glutarate) (PcBG) with dihydroxyl end groups were prepared by polycondensation reactions. Then, dihydroxyl-terminated PcBS and PcBG were used as macroinitiators to initiate ring opening of polymerization of L-lactide toward two series of fully biobased biodegradable PLLA-b-PcBS-b-PLLA and PLLA-b-PcBG-b-PLLA triblock copolymers with PLLA as hard end-blocks. The influences of the midblocks and the endblocks length on microstructure, thermal and tensile properties of the triblock copolymers were studied. Compared to homopolymer PLLA, all the triblock copolymers had a much higher elongation at break with lower tensile strength and tensile modulus, depending on the length of PLLA blocks. It was found that the amorphous PcBG midblock plays a greater role than the crystalline PcBS midblock in enhancing the tensile toughness of ABA triblock copolymers. PLLA-b-PcBG-b-PLLA composed of shorter PLLA hard block displayed typical elastomeric behavior without yield, which is a promising aliphatic polyester-based thermoplastic elastomer. The unsaturated carbon–carbon double bonds in these polyesters backbone provide a variety of opportunities for further modifications.

Gas-Phase Fluorination on PLA Improves Cell Adhesion and Spreading.

For the regeneration or creation of functional tissues, biodegradable biomaterials including polylactic acid (PLA) are widely preferred. Modifications of the material surface are quite common to improve cell–material interactions and thereby support the biological outcome. Typical approaches include a wet chemical treatment with mostly hazardous substances or a functionalization with plasma. In the present study, gas-phase fluorination was applied to functionalize the PLA surfaces in a simple and one-step process. The biological response including biocompatibility, cell adhesion, cell spreading, and proliferation was analyzed in cell culture experiments with fibroblasts L929 and correlated with changes in the surface properties. Surface characterization methods including surface energy and isoelectric point measurements, X-ray photoelectron spectroscopy, and atomic force microscopy were applied to identify the effects of fluorination on PLA. Gas-phase fluorination causes the formation of C–F bonds in the PLA backbone, which induce a shift to a more hydrophilic and polar surface. The slightly negatively charged surface dramatically improves cell adhesion and spreading of cells on the PLA even with low fluorine content. The results indicate that this improved biological response is protein- but not integrin-dependent. Gas-phase fluorination is therefore an efficient technique to improve cellular response to biomaterial surfaces without losing cytocompatibility.