Polymer Ligation Research Articles

The value of mesenteric closure after laparoscopic right hemicolectomy: a scoping review

ObjectiveTo evaluate the prognostic impact and describe suturing tools of mesenteric closure after laparoscopic right hemicolectomy (LRH).MethodsPubMed, Embase, Cochrane library, Web of Science, and Scopus databases, were searched and publications relating to mesenteric closure data and tools were extracted. Search terms: “Mesenteric Defects” and “Mesenteric Closure” were used, and manual searches of eligible articles from literature reference lists performed.ResultA total of 7 publications were identified. 5 focused on prognostic impact and 4 referred to tools for mesenteric closure, two of which concerned both prognostic data and tools. All studies related to prognostic impact were single center with “low” modified GRADE quality. A high degree of heterogeneous was found.ConclusionThe evidence from current research does not support routine closure of mesenteric defects. Use of a polymer ligation clip has produced favorable results in a small sample size trial and further investigation is merited. A large randomized controlled trial is still warranted.

Advancing Performance and Unfolding Mechanism of Lithium and Sodium Storage in SnO2 via Precision Synthesis of Monodisperse PEG‐Ligated Nanoparticles (Adv. Energy Mater. 26/2022)

Nanoreactors In article number 2201015, Shun Wang, Zhiqun Lin and co-workers report the precision crafting of monodisperse PEG-ligated SnO2 nanoparticles using star-like PAA-b-PEG diblock copolymers as nanoreactors which are homogenously anchored on graphene oxide. The surface polymer ligation, precise size control and uniform graphene encapsulation lead to remarkable performance advancement and insights into the mechanism of lithium and sodium storage in SnO2.

Two-colour light activated covalent bond formation

We introduce a photochemical bond forming system, where two colours of light are required to trigger covalent bond formation. Specifically, we exploit a visible light cis/trans isomerization of chlorinated azobenzene, which can only undergo reaction with a photochemically generated ketene in its cis state. Detailed photophysical mapping of the reaction efficiencies at a wide range of monochromatic wavelengths revealed the optimum irradiation conditions. Subsequent small molecule and polymer ligation experiments illustrated that only the application of both colours of light affords the reaction product. We further extend the functionality to a photo reversible ketene moiety and translate the concept into material science. The presented reaction system holds promise to be employed as a two-colour resist.

Advancing Performance and Unfolding Mechanism of Lithium and Sodium Storage in SnO2 via Precision Synthesis of Monodisperse PEG‐Ligated Nanoparticles

AbstractLow conductivity and tin coarsening issues hinder the utility of tin dioxide as anode for lithium and sodium ion batteries. To significantly advance the electrochemical performance and systematically unfold the energy storage mechanism of SnO2, monodisperse poly(ethylene glycol)‐ligated SnO2 nanoparticles are in situ crafted with star‐like poly(acrylic acid)‐block‐poly(ethylene glycol) diblock copolymers as nanoreactors and uniformly confined in layer‐by‐layer stacked graphene oxide matrix (denoted SnO2@PEG‐GO). Remarkably, SnO2@PEG‐GO nanohybrids manifest fully reversible three‐step lithiation‐delithiation reactions of SnO2 with an ultrahigh 100th discharge capacity of 1523 mAh g−1 at 100 mA g−1. Moreover, SnO2@PEG‐GO nanohybrids exhibit an ultrastable sodium storage capacity of 527 mAh g−1 after 500 cycles at 50 mA g−1, and the conversion reaction between Sn and SnO is uncovered as the primary reversible sodiation–desodiation reaction of SnO2. Notably, in addition to buffering volume expansion of SnO2 nanoparticles, the synergy between PEG and GO promotes Li+ or Na+ ion and electron transfers and inhibits Sn coarsening at micro and macro scales. This work provides a robust strategy to realizing outstanding electrochemical properties and scrutinizing fundamental mechanisms that underpin the performance of active materials via surface polymer ligation, precise size control, and uniform graphene encapsulation.

Comparison between Endoloop ligature and Hem-o-lok clip (Polymer ligation) for appendiceal stump closure during laparoscopic appendicectomy

A best evidence topic has been constructed using a described protocol. The three-part question addressed was: In patients undergoing laparoscopic appendicectomy is Hem-o-lok clip safer than Endoloop ligature for closure of appendiceal stump?The search has been devised and 6 studies were deemed to be suitable to answer the question. The outcome assessed was the safety and cost effectiveness of Hem-o-lok clip (Polymer ligation) versus Endoloop ligature for appendiceal stump closure during laparoscopic appendicectomy. We concluded that Hem-o-lok clip is a safe and feasible tool for appendiceal stump closure. It's also a cost-effective way and could be a cheaper option compared to other measures.

Prolonged activity of exenatide: Detailed comparison of Site-specific linear polyglycerol- and poly(ethylene glycol)-conjugates

Exenatide is a small therapeutic peptide being currently used in clinic for the treatment of diabetes mellitus type II, however, displaying a short blood circulation time which makes two daily injections necessary. Covalent polymer modification of a protein is a well-known approach to overcome this limitation, resulting in steric shielding, an increased size and therefore a longer circulation half-life. In this study, we employed site-selective C-terminal polymer ligation of exenatide via copper-catalyzed azide-alkyne-cycloaddition (CuAAC) to yield 1:1-conjugates of either poly(ethylene glycol) (PEG) or linear polyglycerol (LPG) of different molecular weights. Our goal was to compare the impact of the two polymers on size, structure and activity of exenatide on the in vitro and in vivo level. Both polymers did not alter the secondary structure of exenatide and expectedly increased its hydrodynamic size, where the LPG-versions of exenatide showed slightly smaller values than their PEG-analogs of same molecular weight. Upon conjugation, GLP-1 receptor activation was diminished, however, still enabled maximum receptor response at slightly higher concentrations. Exenatide modified with a 40 kDa LPG (Ex-40-LPG) showed significant reduction of the blood glucose level in diabetic mice for up to 72 h, which was comparable to its PEG-analog, but 9-fold longer than native exenatide (8 h).

Randomness and optimality in enhanced DNA ligation with crowding effects

Enzymatic ligation is essential for the synthesis of long DNA. However, the number of ligated products exponentially decays as the DNA synthesis proceeds in a random manner. The controlling of ligation randomness is of importance to suppress exponential decay and demonstrate an efficient synthesis of long DNA. Here, we report the analysis of randomness in sequential DNA ligations, named qPCR-based STatistical Analysis of Randomness (qPCR-bSTAR), by a probability distribution of ligated DNA concentration. We show that the exponential decay is suppressed in a solution of another polymer and DNA ligation is activated at an optimal crowded condition. Theoretical model of kinetic ligation explains that intermolecular attraction due to molecular crowding can be involved in the optimal balance of the ligation speed and the available ligase. Our finding indicates that crowding effects enhance the synthesis of long DNA that retains large genetic information.

A sequential native chemical ligation – thiol-Michael addition strategy for polymer–polymer ligation

Native Chemical Ligation (NCL) between cysteine-terminated polymers and functional thioesters has been employed to prepare functional (co)polymers. The retained thiol functionality at the NCL junction can be exploited for thiol-Michael addition.

Grafting strategies for the synthesis of active DNase I polymer biohybrids

Protein polymer hybrids play an increasingly important role in therapeutics and biocatalysis. Synthesis of these biohybrids can be achieved by either the grafting-from or grafting-to strategy and are generally thought to be interchangeable. Therefore, when choosing between these two strategies the decision is usually based on polymer accessibility and purification preference. However, in this study, we demonstrated that the choice of the polymer ligation strategy played a significant role in the stability and bioactivity of the final hybrid. Our goal was to prepare a thermally stable DNase I polymer hybrid by utilizing either synthetic strategies. We found that the grafting-from strategy using reversible addition-fragmentation chain transfer polymerization (RAFT) or atom transfer radical polymerization (ATRP) yielded DNase I biohybrids with no activity. Control reactions were used to demonstrate inherent protein deactivation caused by the grafting-from conditions for either ATRP or RAFT polymerization. The grafting-to method yielded active and thermally stable DNase I biohybrids.

Visible Light [2 + 2] Cycloadditions for Reversible Polymer Ligation

We introduce visible light induced dynamic covalent chemistry as a powerful reversible ligation tool based on a wavelength-dependent photon efficiency analysis (WPEA). We demonstrate by a monochromatic wavelength scan of the reversible dimerization of styrylpyrene at constant photon count that the system is most effective in its forward reaction at 435 nm, while the highest reverse reaction efficiency is observed at 330 nm. Critically, these optimum wavelengths are not accessible by inspection of the UV/vis spectra of the monomer and the dimer. Application of the identified reaction conditions enabled an entirely λ-orthogonal photoreversible polymer ligation using visible light, including with readily available light sources. The current study thus makes a [2 + 2] reaction system applicable in the critical visible light regime based on quantitative wavelength resolved data for applications in recodeable surface design in biological environments as well as reprogrammable materials systems.

Comparison of the methods of intracorporeal knot and hem-o-lok clip to cover the stumps in laparoscopic appendectomy

Aim: Laparoscopic appendectomy (LA) is used in acute appendicitis treatment in many centers today. Various methods such as intracorporeal knot, endoloop, stapler and hem-o-lok clip are used to close of the appendix stump during LA. All of these methods has several advantages and disadvantages. In this study, we aimed to compare the effect of the intracorporal knot method with hem-o-lok clip method to close of the appendix stump in LA. Material and Methods: Operative data, complications and follow-up results of 143 patients which treated with LA between January 2012 and December 2017 were evaluated retrospectively. Results: Sixty-four patients (44.7%) were males and 79 (55.2%) were females. Seventy-five patients (52.4%) were treated with 2/0 polyglactin (coated vicyrl, ethicon) sutures and 68 patients (47%) were treated with hem-o-lok clip XL (weck hem-o-lok polymer ligation system) for intracorporeal knot to close of the appendix stump. Patients were compared according to the duration of operation, the duration of hospitalization and postoperative complications and there were no statistically significant difference between the data of the cases according to the groups (p = 0.197, p = 0.902, p = 0.503, respectively). Conclusion: We identified that both techniques for appendix stump closure are effective and safe methods in LA.

An integrated model for detecting significant chromatin interactions from high-resolution Hi-C data

Here we present HiC-DC, a principled method to estimate the statistical significance (P values) of chromatin interactions from Hi-C experiments. HiC-DC uses hurdle negative binomial regression account for systematic sources of variation in Hi-C read counts—for example, distance-dependent random polymer ligation and GC content and mappability bias—and model zero inflation and overdispersion. Applied to high-resolution Hi-C data in a lymphoblastoid cell line, HiC-DC detects significant interactions at the sub-topologically associating domain level, identifying potential structural and regulatory interactions supported by CTCF binding sites, DNase accessibility, and/or active histone marks. CTCF-associated interactions are most strongly enriched in the middle genomic distance range (∼700 kb–1.5 Mb), while interactions involving actively marked DNase accessible elements are enriched both at short (<500 kb) and longer (>1.5 Mb) genomic distances. There is a striking enrichment of longer-range interactions connecting replication-dependent histone genes on chromosome 6, potentially representing the chromatin architecture at the histone locus body.

Site-Specific Polymer Attachment to HR2 Peptide Fusion Inhibitors against HIV-1 Decreases Binding Association Rates and Dissociation Rates Rather Than Binding Affinity

A popular strategy for overcoming the limited plasma half-life of peptide heptad repeat 2 (HR2) fusion inhibitors against HIV-1 is conjugation with biocompatible polymers such as poly(ethylene glycol) (PEG). However, despite improved resistance to proteolysis and reduced renal elimination, covalent attachment of polymers often causes a loss in therapeutic potency. In this study, we investigated the molecular origins of the loss in potency upon conjugation of linear, midfunctional, and hyperbranched PEG-like polymers to peptides that inhibit HIV-1-host cell membrane fusion. Fluorescence binding assays revealed that polymer conjugation imparted mass transport limitations that manifested as coexistent slower association and dissociation rates from the gp41 target on HIV-1. Furthermore, reduced association kinetics rather than affinity disruption was responsible for the loss in antiviral potency. Finally, the binding assays indicated that the unmodified HR2-derived peptide demonstrated diffusion-limited binding. The observed high potency of the unmodified peptide in HIV-1 inhibition assays was therefore attributed to rapid peptide conformational changes upon binding to the gp41 prehairpin structure. This study emphasizes that the view in which polymer ligation to therapeutic peptides inadvertently leads to loss in potency due to a loss in binding affinity requires scientific verification on a case-by-case basis and that high peptide potency may be due to rapid target-binding events.

A New Methodology for Assessing Macromolecular Click Reactions and Its Application to Amine--Tertiary Isocyanate Coupling for Polymer Ligation.

Click reactions have provided access to an array of remarkably complex polymer architectures. However, the term “click” is often applied inaccurately to polymer ligation reactions that fail to respect the criteria that typify a true “click” reaction. With the purpose of providing a universal way to benchmark polymer–polymer coupling efficiency at equimolarity and thus evaluate the fulfilment of click criteria, we report a simple one-pot methodology involving the homodicoupling of α-end-functionalized polymers using a small-molecule bifunctional linker. A combination of SEC analysis and chromatogram deconvolution enables straightforward quantification of the coupling efficiency. We subsequently employ this methodology to evaluate an overlooked candidate for the click reaction family: the addition of primary amines to α-tertiary isocyanates (α-tNCO). Using our bifunctional linker coupling strategy, we show that the amine–tNCO reaction fulfills the criteria for a polymer–polymer click reaction, achieving rapid, chemoselective, and quantitative coupling at room temperature without generating any byproducts. We demonstrate that amine–tNCO coupling is faster and more efficient than the more common amine–tertiary active ester coupling under equivalent conditions. Additionally, we show that the α-tNCO end group is unprecedentedly stable in aqueous media. Thus, we propose that the amine–tNCO ligation is a powerful new click reaction for efficient macromolecular coupling.

Peptide-Decorated Dendrimers and Their Bioapplications.

Peptide-decorated dendrimers (PDDs) are a class of spherical, regular, branched polymers that are modified by peptides covalently attached to their surface. PDDs have been used as protein mimetics, novel biomaterials, and in a wide range of biomedical applications. Since their design and development in the late eighties, poly-l-lysine has been a preferred core structure for PDDs. However, numerous recent innovations in polymer synthesis and ligation chemistry have re-energized the field and led to the emergence of well-defined peptide dendrimers with more diverse core structures and functions. This Minireview highlights the development of PDDs driven by significantly improved ligation chemistry incorporating structurally well-defined peptides and the emerging use of PDDs in imaging and drug development.

Practical Analysis of Genome Contact Interaction Experiments.

The three dimensional (3D) architecture of chromosomes is not random but instead tightly organized due to chromatin folding and chromatin interactions between genomically distant loci. By bringing genomically distant functional elements such as enhancers and promoters into close proximity, these interactions play a key role in regulating gene expression. Some of these interactions are dynamic, that is, they differ between cell types, conditions and can be induced by specific stimuli or differentiation events. Other interactions are more structural and stable, that is they are constitutionally present across several cell types. Genome contact interactions can occur via recruitment and physical interaction between chromatin-binding proteins and correlate with epigenetic marks such as histone modifications. Absence of a contact can occur due to presence of insulators, that is, chromatin-bound complexes that physically separate genomic loci. Understanding which contacts occur or do not occur in a given cell type is important since it can help explain how genes are regulated and which functional elements are involved in such regulation. The analysis of genome contact interactions has been greatly facilitated by the relatively recent development of chromosome conformation capture (3C). In an even more recent development, 3C was combined with next generation sequencing and led to Hi-C, a technique that in theory queries all possible pairwise interactions both within the same chromosome (intra) and between chromosomes (inter). Hi-C has now been used to study genome contact interactions in several human and mouse cell types as well as in animal models such as Drosophila and yeast. While it is fair to say that Hi-C has revolutionized the study of chromatin interactions, the computational analysis of Hi-C data is extremely challenging due to the presence of biases, artifacts, random polymer ligation and the huge number of potential pairwise interactions. In this chapter, we outline a strategy for analysis of genome contact experiments based on Hi-C using R and Bioconductor.

Catalyst free visible light induced cycloaddition as an avenue for polymer ligation.

The current study introduces a tetrazole species able to perform a rapid, visible light induced nitrile imine-mediated tetrazole-ene cycloaddition (NITEC). Full conversion of the tetrazole species under mild, catalyst free conditions is reported. Importantly, the visible light ligation technology is applied as a method for the modification and ligation of polymers featuring the rapid, clean and exclusive formation of the desired cycloadduct.

Host–guest accelerated photodimerisation of anthracene-labeled macromolecules in water

The rate enhancement of the [4 + 4]-photodimerisation of anthracene through a host–guest templation strategy in water is presented and applied to polymer ligation and cross-linking. The macrocycle cucurbit[8]uril (CB[8]) tethers together two anthracene moieties in a face-to-face π–π-stack arrangement, which results in significantly faster photochemical dimerisation (on the order of a few minutes) than in the absence of the host, minimises photochemical side reactions and works even under dilute conditions. Therefore, the host-accelerated photodimerisation was applied to macromolecules, shown here for anthracene end-group functionalised poly(ethylene glycol) (PEG) and side-chain functionalised hydroxyethyl cellulose (HEC) to induce polymer-ligation and network-formation (hydrogelation), respectively. In particular, only in the presence of CB[8] did polymer-ligation or chemical cross-linking through photodimerisation occur, whereas photochemical degradation reactions were exclusively observed in the absence of the CB[8] host.

Sequential “Click” Approach to Polyhedral Oligomeric Silsesquioxane-Based Shape Amphiphiles

This paper reports a highly efficient and modular sequential “click” approach for the syntheses of shape amphiphiles based on polymer-tethered polyhedral oligomeric silsesquioxane (POSS). This approach combines both “grafting-to” and “post-functionalization” strategies. It involves the copper-catalyzed Huisgen [3 + 2] cycloaddition (CuAAC) for POSS–polymer ligation and subsequent thiol–ene addition reaction for POSS cage functionalization. Starting from a readily available POSS precursor bearing one alkyne and seven vinyl groups (VPOSS–alkyne), the CuAAC reaction is effective in ensuring the stoichiometric bonding between POSS and azide-functionalized polymers, with no need for fractionation in the purification process. The modularity was demonstrated in two representative polymer systems, hydrophobic polystyrene (PS) and hydrophilic poly(ethylene oxide) (PEO), by the synthesis of VPOSS–PS and VPOSS–PEO. The thiol–ene reaction was subsequently applied to convert all the vinyl groups on the POSS cage quant...

A mechanical Turing machine: blueprint for a biomolecular computer

We describe a working mechanical device that embodies the theoretical computing machine of Alan Turing, and as such is a universal programmable computer. The device operates on three-dimensional building blocks by applying mechanical analogues of polymer elongation, cleavage and ligation, movement along a polymer, and control by molecular recognition unleashing allosteric conformational changes. Logically, the device is not more complicated than biomolecular machines of the living cell, and all its operations are part of the standard repertoire of these machines; hence, a biomolecular embodiment of the device is not infeasible. If implemented, such a biomolecular device may operate in vivo, interacting with its biochemical environment in a program-controlled manner. In particular, it may ‘compute’ synthetic biopolymers and release them into its environment in response to input from the environment, a capability that may have broad pharmaceutical and biological applications.