Amine Residues Research Articles

Polyamines: The valuable bio-stimulants and endogenous signaling molecules for plant development and stress response.

Polyamines (PAs) are nitrogenous and polycationic compounds containing more than two amine residues. Numerous investigations have demonstrated that cellular PA homeostasis plays a key role in various developmental and physiological processes. The PA balance, which may be affected by many environmental factors, is finely maintained by the pathways of PA biosynthesis and degradation (catabolism). In this review, the advances in PA transport and distribution and their roles in plants were summarized and discussed. In addition, the interplay between PAs and phytohormones, NO, and H2O2 were detailed during plant growth, senescence, fruit repining, as well as response to biotic and abiotic stresses. Moreover, it was elucidated how environmental signals such as light, temperature, and humidity modulate PA accumulation during plant development. Notably, PA has been shown to exert a potential role in shaping the domestication of rice. The present review comprehensively summarizes these latest advances, highlighting the importance of PAs as endogenous signaling molecules in plants, and as well proposes future perspectives on PA research.

Designed Polar Cosolvent-Prepared Zinc Oxide Film for Efficient and Stable Inverted Organic Solar Cells.

Here, a simple method of applying dimethylformamide (DMF) as cosolvent in the sol-gel technology is used to improve the quality of ZnO bulk films. First-principles calculations show that with the addition of polar solvent DMF, the adsorption energy (Eads) between the solvent and Zn(OH)₂ increases from -1.42 to -1.74eV, which can stabilize the existence of Zn(OH)₂, thereby promoting the ZnO synthesis. Besides, the elimination of amine residues in the DMF-ZnO film significantly suppress the photocatalytic activity induced by amine-induced coordination or redox reactions. Inverted organic solar cells (OSCs) based on PM6:Y6 and PM6:BTP-eC9 achieves impressive power conversion efficiencies (PCE) of 17.58 and 18.14%, respectively. Furthermore, benefiting from the reduced defects of bulk ZnO, pseudo-bilayer bulk heterojunction (PBHJ) devices based on the optimized ZnO film exhibited superior stability, the PM6:Y6 devices based on DMF-ZnO ETLs can maintain 90.28% of their initial PCE after 1000 h of thermal aging at 85°C, and 80.98% of their initial PCE after 168 h of UV aging. This simple solvent optimization strategy can significantly improve the charge transport of ZnO bulk films, making it a reliable strategy for the preparation of electron transport layers in OSCs.

Synthesis of Nucleoside Selenophosphoramidates via H-Phosphonate Intermediates.

Two synthetic routes for the preparation of nucleoside selenophosphoramidates have been developed by using H-phosphonate derivatives as key substrates. The first method is a one-pot synthesis, which involves the condensation of an amine with H-phosphonate monoesters, mediated by a coupling agent, followed by oxidation with elemental selenium (A). The second approach makes use of the oxidative condensation reaction of H-phosphonoselenoate monoesters with amines promoted by iodine as an oxidizing agent (B). Both methods are efficient and experimentally simple, but the second method (B) seems to be more suited for the synthesis of selenophosphoramidates with bulky or sterically hindered amine residues. It has been shown that both methods also provide a convenient way to produce sulfurized counterparts, i.e., the corresponding thiophosphoramidate derivatives.

CPHEN-017: Comprehensive phenotyping of neutrophil extracellular traps (NETs) on peripheral human neutrophils.

With the recent discovery of their ability to produce neutrophil extracellular traps (NETs), neutrophils are increasingly appreciated as active participants in infection and inflammation. NETs are characterized as large, web-like networks of DNA and proteins extruded from neutrophils, and there is considerable interest in how these structures drive disease in humans. Advancing research in this field is contingent on developing novel tools for quantifying NETosis. To this end, we have developed a 7-marker flow cytometry panel for analyzing NETosis on human peripheral neutrophils following in vitro stimulation, and in fresh circulating neutrophils under inflammatory conditions. This panel was optimized on neutrophils isolated from whole blood and analyzed fresh or in vitro stimulated with phorbol 12-myristate 13-acetate (PMA) or ionomycin, two known NET-inducing agonists. Neutrophils were identified as SSChighFSChighCD15+CD66b+. Neutrophils positive for amine residues and 7-Aminoactinomycin D (7-AAD), our DNA dye of choice, were deemed necrotic (Zombie-NIR+7-AAD+) and were removed from downstream analysis. Exclusion of Zombie-NIR and positivity for 7-AAD (Zombie-NIRdim7-AAD+) was used here as a marker of neutrophil-appendant DNA, a key feature of NETs. The presence of two NET-associated proteins - myeloperoxidase (MPO) and neutrophil elastase (NE) - were utilized to identify neutrophil-appendant NET events (SSChighFSChighCD15+CD66b+Zombie NIRdim7-AAD+MPO+NE+). We also demonstrate that NETotic neutrophils express citrullinated histone H3 (H3cit), are concentration-dependently induced by in vitro PMA and ionomycin stimulation but are disassembled with DNase treatment, and are present in both chronic and acute inflammation. This 7-color flow cytometry panel provides a novel tool for examining NETosis in humans.

Synthesis, molecular dynamics simulation, and evaluation of biological activity of novel flurbiprofen and ibuprofen-like compounds.

The frequent use of anti-inflammatory drugs and the side effects of existing drugs keep the need for new compounds constant. For this purpose, flurbiprofen and ibuprofen-like compounds, which are frequently used anti-inflammatory compounds in this study, were synthesized and their structures were elucidated. Like ibuprofen and flurbiprofen, the compounds contain a residue of phenylacetic acid. On the other hand, it contains a secondary amine residue. Thus, it is planned to reduce the acidity, which is the biggest side effect of NSAI drugs, even a little bit. The estimated ADME parameters of the compounds were evaluated. Apart from internal use, local use of anti-inflammatory compounds is also very important. For this reason, the skin permeability values of the compounds were also calculated. And it has been found to be compatible with reference drugs. The COX enzyme inhibitory effects of the obtained compounds were tested by in vitro experiments. Compound 2a showed significant activity against COX-1 enzyme with an IC50 = 0.123 + 0.005 μM. The interaction of the compound with the enzyme active site was clarified by molecular dynamics studies.

Synthesis and Characterization of Amine and Aldehyde-Containing Copolymers for Enzymatic Crosslinking of Gelatine.

In tissue engineering (TE), the support structure (scaffold) plays a key role necessary for cell adhesion and proliferation. The protein constituents of the extracellular matrix (ECM), such as collagen, its derivative gelatine, and elastin, are the most attractive materials as possible scaffolds. To improve the modest mechanical properties of gelatine, a strategy consists of crosslinking it, as naturally occurs for collagen, which is stiffened by the oxidative action of lysyl oxidase (LO). Here, a novel protocol to crosslink gelatine has been developed, not using the commonly employed crosslinkers, but based on the formation of imine bonds or on aldolic condensation reactions occurring between gelatine and properly synthesized copolymers containing amine residues via LO-mediated oxidation. Particularly, we first synthesized and characterized an amino butyl styrene monomer (5), its copolymers with dimethylacrylamide (DMAA), and its terpolymer with DMAA and acrylic acid (AA). Three acryloyl amidoamine monomers (11a-c) and their copolymers with DMAA were then prepared. A methacrolein (MA)/DMAA copolymer already possessing the needed aldehyde groups was finally developed to investigate the relevance of LO in the crosslinking process. Oxidation tests of amine copolymers with LO were performed to identify the best substrates to be used in experiments of gelatine reticulation. Copolymers obtained with 5, 11b, and 11c were excellent substrates for LO and were employed with MA/DMAA copolymers in gelatine crosslinking tests in different conditions. Among the amine-containing copolymers, that obtained with 5 (CP5/DMMA-43.1) afforded a material (M21) with the highest crosslinking percentage (71%). Cytotoxicity experiments carried out on two cell lines (IMR-32 and SH SY5Y) with the analogous (P5) of the synthetic constituent of M21 (CP5/DMAA) had evidenced no significant reduction in cell viability, but proliferation promotion, thus establishing the biocompatibility of M21 and the possibility to develop it as a new scaffold for TE, upon further investigations.

Self-assembly of water-filled molecular saddles to generate diverse morphologies and high proton conductivity.

The design of single-component organic compounds acting as efficient solid-state proton conduction (SSPC) materials has been gaining significant traction in recent times. Molecular design and controlled self-assembly are critical components in achieving highly efficient SSPC. In this work, we report the design, synthesis, and self-assembly of an organic macrocyclic aza-crown-type compound, P2Mac, which complements synthetic ease with efficient SSPC. P2Mac is derived from the pyridine-2,6-dicarboxamide (PDC) framework and contains polar amide and amine residues in its inner region, while aromatic residues occupy the periphery of the macrocycle. The crystal structure analysis revealed that P2Mac adopts a saddle-shaped geometry. Each P2Mac molecule interacts with one water molecule that is present in its central polar cavity, stabilized by a network of five hydrogen bonds. We could self-assemble P2Mac in a variety of unique, aesthetically pleasing morphologies such as micron-sized octahedra, hexapods, as well as hollow nanoparticles, and microrods. The water-filled polar channels formed through the stacking of P2Mac allow attaining a high proton conductivity value of 21.1 mS cm-1 at 27 °C under a relative humidity (RH) of 95% in the single crystals of P2Mac, while the as-prepared P2Mac pellet sample exhibited about three-orders of magnitude lower conduction under these conditions. The low activation energy of 0.39 eV, calculated from the Arrhenius plot, indicates the presence of the Grotthus proton hopping mechanism in the transport process. This report highlights the pivotal role of molecular design and self-assembly in creating high-performance SSPC organic materials.

Bacterial Flagellum-Drug Nanoconjugates for Carrier-Free Immunochemotherapy.

The combination of immunotherapy and chemotherapy to ablate tumors has attracted substantial attention due to the ability to simultaneously elicit antitumor immune responses and trigger direct tumor cell death. However, conventional combinational strategies mainly focus on the employment of drug carriers to deliver immunomodulators, chemotherapeutics, or their combinations, always suffering from complicated preparation and carrier-relevant side effects. Here, the fabrication of bacterial flagellum-drug nanoconjugates (FDNCs) for carrier-free immunochemotherapy is described. FDNCs are simply prepared by attaching chemotherapeutics to amine residues of flagellin through an acid-sensitive and traceless cis-aconityl linker. By virtue of native nanofibrous structure and immunogenicity, bacterial flagella not only show long-term tumor retention and highly efficient cell internalization, but also provoke robust systemic antitumor immune responses. Meanwhile, conjugated chemotherapeutics exhibit an acid-mediated release profile and durable intratumoral exposure, which can induce potent tumor cell inhibition via direct killing. More importantly, this combination is able to augment immunoactivation effects associated with chemotherapy-enabled immunogenic tumor cell death to further enhance antitumor efficacy. By leveraging the innate response of the immune system to pathogens, the conjugation of therapeutic agents with self-adjuvant bacterial flagella provides an alternative approach to develop carrier-free nanotherapeutics for tumor immunochemotherapy.

Poly(Oxanorbornene)-Protein Conjugates Prepared by Grafting-to ROMP as Alternatives for PEG.

PEGylation is the gold standard in protein-polymer conjugation, improving circulation half-life of biologics while mitigating the immune response to a foreign substance. However, preexisting anti-PEG antibodies in healthy humans are becoming increasingly prevalent and elicitation of anti-PEG antibodies when patients are administered with PEGylated therapeutics challenges their safety profile. In the current study, two distinct amine-reactive poly(oxanorbornene) (PONB) imide-based water-soluble block co-polymers are synthesized using ring-opening metathesis polymerization (ROMP). The synthesized block-copolymers include PEG-based PONB-PEG and sulfobetaine-based PONB-Zwit. The polymers are then covalently conjugated to amine residues of lysozyme (Lyz) and urate oxidase (UO) using a grafting-to bioconjugation technique. Both Lyz-PONB and UO-PONB conjugates retained significant bioactivities after bioconjugation. Immune recognition studies of UO-PONB conjugates indicated a comparable lowering of protein immunogenicity when compared to PEGylated UO. PEG-specific immune recognition is negligible for UO-PONB-Zwit conjugates, as expected. These polymers provide a new alternative for PEG-based systems that retain high levels of activity for the biologic while showing improved immune recognition profiles.

Facile Synthesis of Catechol-Containing Polyacrylamide Copolymers: Synergistic Effects of Amine, Amide and Catechol Residues in Mussel-Inspired Adhesives.

The straightforward synthesis of polyamide-derived statistical copolymers with catechol, amine, amide and hydroxy residues via free radical polymerization is presented. In particular, catechol, amine and amide residues are present in natural mussel foot proteins, enabling strong underwater adhesion due to synergistic effects where cationic residues displace hydration and ion layers, followed by strong short-rang hydrogen bonding between the catechol or primary amides and SiO2 surfaces. The present study is aimed at investigating whether such synergistic effects also exist for statistical copolymer systems that lack the sequence-defined positioning of functional groups in mussel foot proteins. A series of copolymers is established and the adsorption in saline solutions on SiO2 is determined by quartz crystal microbalance measurements and ellipsometry. These studies confirm a synergy between cationic amine groups with catechol units and primary amide groups via an increased adsorptivity and increased polymer layer thicknesses. Therefore, the free radical polymerization of catechol, amine and amide monomers as shown here may lead to simplified mussel-inspired adhesives that can be prepared with the readily scalable methods required for large-scale applications.

Synthesis of Cystine-Stabilised Dicarba Conotoxin EpI: Ring-Closing Metathesis of Sidechain Deprotected, Sulfide-Rich Sequences.

Recombinant peptide synthesis allows for large-scale production of peptides with therapeutic potential. However, access to dicarba peptidomimetics via sidechain-deprotected sequences becomes challenging with exposed Lewis basicity presented by amine and sulfur-containing residues. Presented here is a combination of strategies which can be used to deactivate coordinative residues and achieve high-yielding Ru-catalyzed ring-closing metathesis. The chemistry is exemplified using α-conotoxin EpI, a native bicyclic disulfide-containing sequence isolated from the marine conesnail Conus episcopatus. Replacement of the loop I disulfide with E/Z-dicarba bridges was achieved with high conversion via solution-phase ring-closing metathesis of the unprotected linear peptide after simple chemoselective oxidation and ion-exchange masking of problematic functionality. Metathesis was also attempted in green solvent choices to further improve the sustainability of dicarba peptide synthesis.

Late-Stage, Stereoretentive, and Site-Selective Modification of Synthetic Peptides by Using Photoredox Catalysis.

Late-stage functionalisation is an attractive method to generate peptide analogues containing non-natural residues. It is shown that cysteine residues can be activated as Crich-type thioethers, either by alkylation of a synthetic cysteine-continuing peptide or by incorporation of a modified cysteine unit into solid phase or solution phase peptide synthesis. Photoredox catalysed reaction of the thioether generates an alanyl radical intermediate in a stereoretentive and site-selective manner, even in the presence of free cysteine residues. The radical can react with non-activated alkenes to form non-natural residues bearing aliphatic, hydrophobic units. A method to avoid unwanted alkylation of amine residues was identified and the process was applied to the functionalization of both linear and cyclic synthetic peptides.

Синтез производных N-(5-(метилсульфанил)- 4H-1,2,4-триазол-3-ил)пиридин-2-амина и их 1,2,4-триазиновых предшественников

A solvent-free interaction between 5-cyano-1.2.4-triazines and 5-methylsulfanyl-4H-1,2,4-triazol-3-amines has been studied. The structure of the product of ipso-substitution of cyano-group with the corresponding heterocyclic amine residue has been proven by 1Н NMR and ESI-MS data. Thus, in the 1Н NMR spectra a three-proton singlet at 2.61 ppm is present, which can be interpreted as the signal of the methylsulfanyl group protons. Subsequent transformation of 1,2,4-triazine scaffold of the resulting product into a pyridine one has been successfully per-formed under autoclave conditions. It has been found that methylsulfanyl group undergoes no transformations in both stages of synthesis. This fact is also proven by X-Ray crystallography data of the obtained functionalised bypyridines. According to the X-Ray crystallography data, compound 4 crystallizes as two crystallographically independent molecules in non-centrosymmetric space group P-1 with triclinic system. The crystal structure is formed by numerous intermolecular N∙∙∙H contacts between two crystallographically independent molecules of triazolylpyridine-2-amine. The 1Н NMR spectra of compound 4 contain two doublets of the new pyridine cycle at 7.37 and 7.61 ppm. Thus, properties of 5-methysulfanyl-4H-1,2,4-triazol-3-amine are different from these of its analogue with mercaptogroup at C5 position. Namely, in accordance to our previous results ipso-substitution of C5-cyanogroup of 1,2,4-triazine with moiety of the latter amine is accompanied by desulfurization reaction.

Single stop analysis of a protein surface using molecular probe electrochemistry.

Visualization of a protein in its native form and environment without any interference has always been a challenging task. Contrary to the assumption that protein surfaces are smooth, they are in fact highly irregular with undulating surfaces. Hence, in this study, we have tackled this ambiguous nature of the 'surface' of a protein by considering the 'effective' protein surface (EPS) with respect to its interaction with the geometrically well-defined and structurally inert anionic molecule [3,3'-Co(1,2-C2B9H11)2]-, abbreviated as [o-COSAN]-, whose stability, propensity for amine residues, and self-assembling abilities are well reported. This study demonstrates the intricacies of protein surfaces exploiting simple electrochemical measurements using a 'small molecule' redox-active probe. This technique offers the advantage of not utilizing any harsh experimental conditions that could alter the native structure of the protein and hence the protein integrity is retained. Identification of the amino acid residues which are most involved in the interactions with [3,3'-Co(1,2-C2B9H11)2]- and how a protein's environment affects these interactions can help in gaining insights into how to modify proteins to optimize their interactions particularly in the fields of drug design and biotechnology. In this research, we have demonstrated that [3,3'-Co(1,2-C2B9H11)2]- anionic small molecules are excellent candidates for studying and visualizing protein surfaces in their natural environment and allow proteins to be classified according to the surface composition, which imparts their properties. [3,3'-Co(1,2-C2B9H11)2]- 'viewed' each protein surface differently and hence has the potential to act as a simple and easy to handle cantilever for measuring and picturing protein surfaces.

A Novel Bifunctional Nanoplatform with Aggregation-Induced Emission Property for Efficient Photodynamic Killing of Bacteria and Wound Healing.

Photodynamic antimicrobial therapy (PDAT) has been extensively studied because of its potential applications such as precise controllability, high spatiotemporal accuracy, and non-invasiveness. More importantly, it is difficult for bacteria to develop resistance to the aforementioned PDATs. However, the selectivity of traditional PDAT methods to bacteria is generally poor, so it has been proposed to introduce positively charged components such as quaternary ammonium salts to enhance the targeting of bacteria; however, they always possess high toxicity to normal cells. As a result, measures should be taken to enhance the targeting of bacteria and avoid side effects on normal cells. In our work, we creatively design a nanoplatform with high anti-bacterial efficiency, low side effects and its size is approximately 121 nm. BSA, as a nanocarrier, encapsulates the photosensitizer (E)-4-(4-(diphenylamino)styryl)-1-methylpyridin-1-ium with AIE properties named as BSA-Tpy, which increases its circulation time in vivo and improves the biocompatibility. Under acidic conditions (pH = 5.0), the surface positive charge of the BSA-Tpy is increased to +18.8 mV due to protonation of amine residues to achieve the targeting effect on bacteria. Besides, under the irradiation of white light, the BSA-Tpy will produce ROS to kill bacteria efficiently about 99.99% for both Gram-positive and Gram-negative bacteria, which shows the potential application value for the treatment of infected wounds. We have developed a feasible method for photodynamic antibacterial therapy, possessing excellent biocompatibility and high antibacterial efficiency with good fluorescence imaging property.

Hyperbranched Poly(β-amino ester)s (HPAEs) Structure Optimisation for Enhanced Gene Delivery: Non-Ideal Termination Elimination

Many polymeric gene delivery nano-vectors with hyperbranched structures have been demonstrated to be superior to their linear counterparts. The higher delivery efficacy is commonly attributed to the abundant terminal groups of branched polymers, which play critical roles in cargo entrapment, material-cell interaction, and endosome escape. Hyperbranched poly(β-amino ester)s (HPAEs) have developed as a class of safe and efficient gene delivery vectors. Although numerous research has been conducted to optimise the HPAE structure for gene delivery, the effect of the secondary amine residue on its backbone monomer, which is considered the non-ideal termination, has never been optimised. In this work, the effect of the non-ideal termination was carefully evaluated. Moreover, a series of HPAEs with only ideal terminations were synthesised by adjusting the backbone synthesis strategy to further explore the merits of hyperbranched structures. The HPAE obtained from modified synthesis methods exhibited more than twice the amounts of the ideal terminal groups compared to the conventional ones, determined by NMR. Their transfection performance enhanced significantly, where the optimal HPAE candidates developed in this study outperformed leading commercial benchmarks for DNA delivery, including Lipofectamine 3000, jetPEI, and jetOPTIMUS.

Tyrosinase-Mediated Synthesis of Nanobody-Cell Conjugates.

A convenient enzymatic strategy is reported for the modification of cell surfaces. Using a tyrosinase enzyme isolated from Agaricus bisporus, unique tyrosine residues introduced at the C-termini of nanobodies can be site-selectively oxidized to reactive o-quinones. These reactive intermediates undergo rapid modification with nucleophilic thiol, amine, and imidazole residues present on cell surfaces, producing novel nanobody–cell conjugates that display targeted antigen binding. We extend this approach toward the synthesis of nanobody–NK cell conjugates for targeted immunotherapy applications. The resulting NK cell conjugates exhibit targeted cell binding and elicit targeted cell death.

A Review Study of the Influences of Dendrimer Nanoparticles on Stored Platelet in Order to Treat Patients (2001-2020)

Background: Platelets are sensitive to chilling, so the optimal storage temperature for maintaining normal function and structure in platelets is 22-24 °C up to 3-5 days. Introduction: Platelets are important blood cells involved in immunity, inflammation, and thrombosis. Today, platelet products are widely used to prevent bleeding in patients with thrombocytopenia and coagulopathy disorders. As a result, maintaining the quality of these products is very important. Method: In this review study, the reported influences of various dendrimers on platelets from 2001 to 2020 were investigated. Result: The results showed that positively charged dendrimers can cause platelet aggregation and activation during platelet storage time through their amine residues. In addition to surface charge, high generations, molecular weight and concentration are not recommended in the field of platelet storage and treatment. In contrast, negatively charged dendrimers, usually used at lower generations with proper molecular weight, lower size (less than 100 nm) and their carboxyl residues, cannot induce adverse effects on platelets during storage time. In addition, the results of this study revealed that PEGylation of dendrimers and platelets can improve platelet storage conditions. Conclusion: As anionic dendrimers can improve platelet storage time without inducing significant changes in morphology and function of platelets, they are recommended in the field of platelet storage and treatment.

Sortase-mediated immobilization of Candida antarctica lipase B (CalB) on graphene oxide; comparison with chemical approach

In this study, Candida antarctica lipase B (CalB) was covalently immobilized on the surface of graphene oxide (GO) nanoparticles by sortase-mediated immobilization as well as a chemical attachment approach. Sortase is a transpeptidase that provides one-step purification and targeted immobilization of CalB from one specific site, presenting oriented attachment of the enzyme to a solid support. Chemical immobilization, on the other hand, is considered as a random immobilization, in which the protein can bind to the support from different regions of the protein surface. In this approach, amine-functionalized GO was further modified with glutaraldehyde to facilitate the covalent binding of CalB via its amine residues. The applied methods produced 60% and 100% immobilization yields and presented 0.106 U/mg and 0.085 U/mg of specific activities for the oriented and random immobilization, respectively. The stabilized enzyme with the sortase-mediated approach retained approximately 80% of its initial activity at 50°C.

Glycogen synthase downregulation rescues the amylopectinosis of murine RBCK1 deficiency.

Longer glucan chains tend to precipitate. Glycogen, by far the largest mammalian glucan and the largest molecule in the cytosol with up to 55 000 glucoses, does not, due to a highly regularly branched spherical structure that allows it to be perfused with cytosol. Aberrant construction of glycogen leads it to precipitate, accumulate into polyglucosan bodies that resemble plant starch amylopectin and cause disease. This pathology, amylopectinosis, is caused by mutations in a series of single genes whose functions are under active study toward understanding the mechanisms of proper glycogen construction. Concurrently, we are characterizing the physicochemical particularities of glycogen and polyglucosans associated with each gene. These genes include GBE1, EPM2A and EPM2B, which respectively encode the glycogen branching enzyme, the glycogen phosphatase laforin and the laforin-interacting E3 ubiquitin ligase malin, for which an unequivocal function is not yet known. Mutations in GBE1 cause a motor neuron disease (adult polyglucosan body disease), and mutations in EPM2A or EPM2B a fatal progressive myoclonus epilepsy (Lafora disease). RBCK1 deficiency causes an amylopectinosis with fatal skeletal and cardiac myopathy (polyglucosan body myopathy 1, OMIM# 615895). RBCK1 is a component of the linear ubiquitin chain assembly complex, with unique functions including generating linear ubiquitin chains and ubiquitinating hydroxyl (versus canonical amine) residues, including of glycogen. In a mouse model we now show (i) that the amylopectinosis of RBCK1 deficiency, like in adult polyglucosan body disease and Lafora disease, affects the brain; (ii) that RBCK1 deficiency glycogen, like in adult polyglucosan body disease and Lafora disease, has overlong branches; (iii) that unlike adult polyglucosan body disease but like Lafora disease, RBCK1 deficiency glycogen is hyperphosphorylated; and finally (iv) that unlike laforin-deficient Lafora disease but like malin-deficient Lafora disease, RBCK1 deficiency's glycogen hyperphosphorylation is limited to precipitated polyglucosans. In summary, the fundamental glycogen pathology of RBCK1 deficiency recapitulates that of malin-deficient Lafora disease. Additionally, we uncover sex and genetic background effects in RBCK1 deficiency on organ- and brain-region specific amylopectinoses, and in the brain on consequent neuroinflammation and behavioural deficits. Finally, we exploit the portion of the basic glycogen pathology that is common to adult polyglucosan body disease, both forms of Lafora disease and RBCK1 deficiency, namely overlong branches, to show that a unified approach based on downregulating glycogen synthase, the enzyme that elongates glycogen branches, can rescue all four diseases.