Covalent Reaction Research Articles

N-terminal domain of tyrosyl-DNA phosphodiesterase I regulates topoisomerase I-induced toxicity in cells

Tyrosyl-DNA phosphodiesterase I (Tdp1) hydrolyzes phosphodiester-linked adducts from both ends of DNA. This includes the topoisomerase I (TOP1)-DNA covalent reaction intermediate that is the target of the camptothecin class of chemotherapeutics. Tdp1 two-step catalysis is centered on the formation of a Tdp1-DNA covalent complex (Tdp1cc) using two catalytic histidines. Here, we examined the role of the understudied, structurally undefined, and poorly conserved N-terminal domain (NTD) of Tdp1 in context of full-length protein in its ability to remove TOP1cc in cells. Using toxic Tdp1 mutants, we observed that the NTD is critical for Tdp1’s ability to remove TOP1-DNA adducts in yeast. Full-length and N-terminal truncated Tdp1 mutants showed similar expression levels and cellular distribution yet an inversed TOP1-dependent toxicity. Single turnover catalysis was significantly different between full-length and truncated catalytic mutants but not wild-type enzyme, suggesting that Tdp1 mutants depend on the NTD for catalysis. These observations suggest that the NTD plays a critical role in the regulation of Tdp1 activity and interaction with protein-DNA adducts such as TOP1cc in cells. We propose that the NTD is a regulatory domain and coordinates stabilization of the DNA-adducted end within the catalytic pocket to access the phosphodiester linkage for hydrolysis.

Activated wood surface and functionalized cellulose co-building strong chemical wood bonding performance

Herein, an activated wood surface rich in CHO groups was constructed by spraying a sodium periodate aqueous solution on a natural wood surface. Besides, microcrystalline cellulose was functionalized to obtain aminated cellulose, which was dissolved in an aqueous solution and used as a specific adhesive. Subsequently, an ultrastrong wood bonding interface was co-constructed with the activated wood surface and aminated cellulose, which was formed by a chemical covalent reaction between aldehyde groups at the activated wood interface and amino groups on aminated cellulose. The dry, hot-water, and boiling-water lap shear strengths of the plywood specimens were 1.47, 1.07, and 1.08 MPa, respectively. The boiling-water strength of the plywood made from the activated wood surface achieved increased to 1.08 MPa from 0 MPa of the plywood constructed on the nonactivated wood surface. The chemical crosslinking reaction and bonding mechanism between the adhesive and activated wood surface were clarified by density functional theory calculations, attenuated total reflectance–Fourier-transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The results showed that chemical bonding (aminal NCN and imine CN) at the bonding interface played an important part in improving the water resistance and bonding strength. This work provides new concepts for designing durable and moisture-resistant wood products.

Synergy of Ion Exchange and Covalent Reaction: Immobilization of Penicillin G Acylase on Heterofunctional Amino-Vinyl Sulfone Agarose

Agarose-vinyl sulfone (VS) beads have proven to be a good support to immobilize several enzymes. However, some enzymes are hardly immobilized on it. This is the case of penicillin G acylase (PGA) from Escherichia coli, which is immobilized very slowly on this support (less than 10% in 24 h). This enzyme is also not significantly adsorbed in aminated MANAE-agarose beads, an anionic exchanger. In this study, MANAE-agarose beads were modified with divinyl sulfone (DVS) to produce MANAE-vinyl sulfone (VS) agarose beads. When PGA was immobilized on this support, the enzyme was fully immobilized in less than 1.5 h. PGA cannot be released from the support by incubation at high ionic strength, suggesting that the enzyme was rapidly immobilized in a covalent fashion. Considering that the amount of reactive VS groups was only marginally increased, the results indicated some cooperative effect between the anion exchange on the amine groups of the support, probably as the first step of the process, and the covalent attachment of the previously adsorbed PGA molecules. The covalent reaction of the previously adsorbed enzyme molecules proceeds much more efficiently than that of the free enzyme, due to the proximity of the reactive groups of the support and the enzyme. Finally, the steps of immobilization, incubation, and blocking with different agents were studied to determine the effects on final activity/stability. The stability of PGA immobilized on this new catalyst was improved with respect to the VS-agarose prepared at low ionic strength.

Light controlled reversible Michael addition of cysteine: a new tool for dynamic site-specific labeling of proteins.

Cysteine-based Michael addition is a widely employed strategy for covalent conjugation of proteins, peptides, and drugs. The covalent reaction is irreversible in most cases, leading to a lack of control over the process. Utilizing spectroscopic analyses along with X-ray crystallographic studies, we demonstrate Michael addition of an engineered cysteine residue in human Cellular Retinol Binding Protein II (hCRBPII) with a coumarin analog that creates a non-fluorescent complex. UV-illumination reverses the conjugation, yielding a fluorescent species, presumably through a retro-Michael process. This series of events can be repeated between a bound and non-bound form of the cysteine reversibly, resulting in the ON-OFF control of fluorescence. The details of the mechanism of photoswitching was illuminated by recapitulation of the process in light irradiated single crystals, confirming the mechanism at atomic resolution.

Deep generative design of porous organic cages via a variational autoencoder.

Porous organic cages (POCs) are a class of porous molecular materials characterised by their tunable, intrinsic porosity; this functional property makes them candidates for applications including guest storage and separation. Typically formed via dynamic covalent chemistry reactions from multifunctionalised molecular precursors, there is an enormous potential chemical space for POCs due to the fact they can be formed by combining two relatively small organic molecules, which themselves have an enormous chemical space. However, identifying suitable molecular precursors for POC formation is challenging, as POCs often lack shape persistence (the cage collapses upon solvent removal with loss of its cavity), thus losing a key functional property (porosity). Generative machine learning models have potential for targeted computational design of large functional molecular systems such as POCs. Here, we present a deep-learning-enabled generative model, Cage-VAE, for the targeted generation of shape-persistent POCs. We demonstrate the capacity of Cage-VAE to propose novel, shape-persistent POCs, via integration with multiple efficient sampling methods, including Bayesian optimisation and spherical linear interpolation.

Computational study on the mechanisms of inhibition of SARS-CoV-2 Mpro by aldehyde warheads based on DFT.

SARS-CoV-2 main protease, Mpro, plays a crucial role in the virus replication cycle, making it an important target for antiviral research. In this study, a simplified model obtained through truncation is used to explore the reaction mechanism of aldehyde warhead compounds inhibiting Mpro at the level of density functional theory. According to the calculation results, proton transfer (P_T)-nucleophilic attack (N_A) is the rate-determining step in the entire reaction pathway. The water molecule that plays a catalytic role occupies the oxyanion hole, which is unfavorable for the aldehyde warhead to approach the Cys145 SH. Through a hypothetical study of substituting the main chain NH with methylene, it is further confirmed that the P_T-N_A is a proton transfer-dominated process accompanied by a nucleophilic attack reaction. In this process, the oxyanion hole serves only to stabilize the aldehyde oxygen anion and therefore does not have a significant impact on the activation free energy barrier of the step. Our research results provide a unique perspective for understanding the covalent inhibition reaction of the Mpro active site. This study also offers theoretical guidance for the design of new Mpro covalent inhibitors.

Dual reactivity based dynamic covalent chemistry: mechanisms and applications.

Dynamic covalent chemistry (DCC) focuses on the reversible formation, breakage, and exchange of covalent bonds and assemblies, setting a bridge between irreversible organic synthesis and supramolecular chemistry and finding wide utility. In order to enhance structural and functional diversity and complexity, different types of dynamic covalent reactions (DCRs) are placed in one vessel, encompassing orthogonal DCC without crosstalk and communicating DCC with a shared reactive functional group. As a means of adding tautomers, widespread in chemistry, to interconnected DCRs and combining the features of orthogonal and communicating DCRs, a concept of dual reactivity based DCC and underlying structural and mechanistic insights are summarized. The manipulation of the distinct reactivity of structurally diverse ring-chain tautomers allows selective activation and switching of reaction pathways and corresponding DCRs (C-N, C-O, and C-S) and assemblies. The coupling with photoswitches further enables light-mediated formation and scission of multiple types of reversible covalent bonds. To showcase the capability of dual reactivity based DCC, the versatile applications in dynamic polymers and luminescent materials are presented, paving the way for future functionalization studies.

Fluoride-regulated colorimetric and fluorometric switch through B–F dynamic covalent reactions of AIEgens

A rational design strategy was proposed by introducing borate units into AIE-active molecular skeletons to achieve fluoride-regulated colorimetric and fluorometric switch based on B–F dynamic covalent reactions.

Graphene oxide-based large-area dynamic covalent interfaces.

Dynamic materials, being capable of reversible structural adaptation in response to the variation of external surroundings, have experienced significant advancements in the past several decades. In particular, dynamic covalent materials (DCMs), where the dynamic covalent bonds (DCBs) can reversibly break and reform under defined conditions, present superior dynamic characteristics, such as self-adaptivity, self-healing and shape memory. However, the dynamic characteristics of DCBs are mainly limited within the length scale of covalent bonds, due to the local position exchange or the inter-distance variation between the chemical compositions involved in the reversible covalent reactions. In this minireview, a discussion regarding the realization of long-range migration of chemical compositions along the interfaces of graphene oxide (GO)-based materials via the spatially connected and consecutive occurrence of DCB-based reversible covalent reactions is presented, and the interfaces are termed "large-area dynamic covalent interfaces (LDCIs)". The effective strategies, including water adsorption, interfacial curvature and metal-substrate support, as well as the potential applications of LDCIs in water dissociation and humidity sensing are summarized. Additionally, we also give an outlook on potential strategies to realize LDCIs on other 2D carbon-based materials, including the interfacial morphology and periodic element doping. This minireview provides insights into the realization of LDCIs on a wider range of 2D materials, and offers a theoretical perspective for advancing materials with long-range dynamic characteristics and improved performance, including controlled drug delivery/release and high-efficiency (bio)sensing.

Competitive binding of maltodextrin and pectin at the interface of whey protein hydrolyzate-based fish oil emulsion under high temperature sterilization: Effects on storage stability and in vitro digestion

Whey protein hydrolysate (WPH), maltodextrin (MD), low methoxy pectin (LMP) and high methoxy pectin (HMP) were used to study the interface binding under high temperature sterilization conditions (121 °C, 15 min). The effect of competitive binding of MD and pectin with interface protein on the storage stability and gastrointestinal fate of fish oil emulsion was studied. The low-molecular-weight MD and the interface protein undergo a wide range of covalent binding through the Maillard reaction, while a small amount of high-molecular-weight pectin can form a protective shell with the interface protein through electrostatic interaction to inhibit the covalent reaction of MD, which was called competitive binding. However, due to the bridging and depletion flocculation of pectin, the emulsification stability of fish oil emulsion reduced. After 13 days of storage, compared with the particle size of the WPH fish oil emulsion (459.18 nm), the fish oil emulsion added with LMP and HMP reached 693.58 nm and 838.54 nm, respectively. In vitro digestion proved that WPH fish oil emulsion flocculated rapidly in the stomach (1.76 μm), while WPH-MD and WPH-MD-pectin fish oil emulsions flocculated slightly (less than800 nm). WPH-MD-pectin delayed digestion in the gastrointestinal tract, and HMP exhibited a better slow-release effect. This study provides reference for the design of multi-component functional drinks and other bioactive ingredient delivery system.

Bioinspired polydopamine-mediated metal-organic framework click-grafting aptamers functionalized fabric for highly-specific recognition of microcystin-leucine arginine

Fabricating functional electrospun nanofiber coating for highly selective extraction of microcystin-LR (MC-LR) was of significant importance for water-safety monitoring. Herein, a novel MOF@aptamer functionalized nanofabric was presented via a facile and reliable strategy integrating polydopamine (PDA) mediation and thiol-ene chemistry and applied for specific recognition of the MC-LR model analyte. Using polydopamine (PDA) as the mediating layer, vinyl-UiO-66 MOF was grown in situ, followed by post-synthetic modification (PSM) of Zr4+ with vinyl phosphate and rapid UV-initiated click reaction of aptamers. Uniform deposition of Zr-based MOF (vinyl-UiO-66) on the nanofibers was directly produced, and the tedious co-electrospinning process was abandoned to prevent the aggregation and encapsulation of MOF. Via an efficient “thiol-ene” chemistry, massive thiol-terminated aptamers were grafted on MOF within one step under friendly conditions, rather than the time-consuming nanoparticle adsorption or unfriendly covalent chemical reactions. As a result, the robust MOF@aptamer-coated nano-fabrics were obtained, and a highly selective performance towards MC-LR was illustrated with a limit of detection (LOD) at 0.002 ng/mL, good precision (CV<8.3%), good repeatability (2.2∼6.0%) when coupled with LC-MS. Almost 1∼2 orders of magnitude higher detection sensitivity was exhibited than that of the common non-specific SPE/SPME fiber reported so far. Applied to water samples, the good matrix-resistance ability, and acceptable recovery yields were achieved with high specificity. This strategy might provide a rapid and friendly protocol to efficiently fabricate MOF@aptamer functionalized nano-fabrics through electrospinning and interfacial "thiol-ene" chemistry for highly-selective microextraction.

Alkaline Phosphatase-Controllable and Red Light-Activated RNA Modification Approach for Precise Tumor Suppression.

RNA interference (RNAi) has proved to be a promising modality for disease treatment. However, the promise of conventional RNA therapeutics for clinical application is severely impeded by low delivery efficiency and susceptibility of RNAs to serum RNases. Therefore, developing advanced RNAi technology is an increasing demand for achieving precise medicine. Herein, for the first time, we propose an alkaline phosphatase (ALP)-controllable and red light-activated RNA modification (ALARM) approach for anti-tumor therapeutic application. An ALP-responsive NIR fluorogenic probe f-RCP consisting of a tumor-targeting cyclic RGD peptide, an ALP-activated photosensitizer CyOP, and an 1O2-susceptible furan module for RNA modification was rationally designed and synthesized. Studies have demonstrated that f-RCP can specifically target to liver carcinoma HepG2 cells and spontaneously emit activated NIR/photoacoustic signals upon cleavage by the ALP enzyme, allowing for sensitive detection of ALP-positive tumors. More notably, we surprisingly found that the capability of f-RCP producing singlet oxygen (1O2) under red light irradiation could be simultaneously unlocked, which can ignite the covalent cyclization reaction between furan and nucleobases of intracellular RNA molecules, leading to significant mitochondrial damage and severe apoptosis of tumor cells, in consequence realizing efficient tumor suppression. Most importantly, the potential therapeutic mechanism was first explored on the transcriptomic level. This delicate ALARM strategy may open up new insights into cancer gene therapy.

Novel ultrastrong wood bonding interface through chemical covalent crosslinking of aldehyde-amine

In this work, a new concept for a chemical wood bonding interface is proposed. Through interface tailoring, the synergistic interaction between wood interface and polyamine (PA xn , indicating the PA xn has x terminal groups) adhesive was created. The bonding strength and water resistance of the proposed chemical wood bonding interface were evaluated. An activated wood interface with abundant -CHO groups was constructed via spraying with an aqueous NaIO 4 solution. The lap shear strengths of these activated wood interfaces using PA 4n , PA 5n , PA 6n , PA 7n adhesives were 0.84, 0.98, 1.85, 1.96 MPa, respectively, after a “4 + 4 + 1″ harsh test (soak the plywood specimens in boiling water for 4.0 h, then dry in oven for 20 h, soak again in boiling water for 4.0 h, and then soak in cold water for 1.0 h). These results indicate super-strong bonding performance and water resistance. In order to explore the bonding mechanism of the proposed chemical wood bonding interface, wood cell walls in the active gluing region of plywood were characterized on the nanoscale using AFM and SEM. XPS was used to clarify the chemical covalent cross-linking reaction between the PA xn adhesive and the activated wood interface. The results demonstrated that the chemical bonding (imine C N and aminal N-C-N) at the wood: adhesive interface plays a decisive role in the improvement of bonding strength and water resistance. In summary, a novel wood bonding system dominated by adhesive-wood covalent linkages was constructed based on an activated wood interface and specific polyamine adhesives under a relatively low hot-pressing temperature (110 °C). This work provides new insights into how to design an unbreakable, moisture-proof, and highly durable bonding interface for wood-based materials. Schematic diagram for the design and development of ultrastrong wood bonding interface via chemical bonding. • A new concept for a chemical wood bonding interface is proposed. • A novel wood bonding system dominated by adhesive-wood covalent linkages was constructed. • The bonding mechanism between wood interface and adhesive was clarified. • The new wood composite has excellent bonding strength and water resistance

Thermomechanical analysis (TMA) of vitrimers

Vitrimers are an exciting class and new generation of polymer materials combining the strength of a traditional thermoset polymer with the reprocessability of a traditional thermoplastic polymer. However, a key debate in literature has surrounded the best method to identify the vitrimer topology freezing temperature (Tv), above which dynamic covalent bond exchange reactions occur, allowing for self-healing, recycling, and shape reconfigurability of vitrimers. While common methods in literature to identify the Tv include stress relaxation, creep, and fluorescence, we herein validate thermomechanical analysis (TMA) as a reliable method for Tv identification. TMA provides several clear advantages as it is less time and sample intensive than stress relaxation. Furthermore, it is performed in compression to match application conditions, provides more consistent results than creep, and identifies the coefficient of thermal expansion (α). We demonstrate that expansion TMA is a valuable tool in Tv identification by validating several clearly accepted trends in literature; TMA validates that the Tv increases with decreasing catalyst concentration and increasing heating rate while showing negligible variation with increasing applied force. Finally, we report an increasing α with increasing catalyst concentration for our vitrimer material. By taking advantage of such a fast and reliable method to identify Tv, we believe this fundamental study will support future vitrimer research.

Reversible Single-Crystal-to-Single-Crystal Transformation of a Coordination Polymer through Solar-Switchable Cycloaddition and Cycloreversion Reaction.

Reversible covalent reactions within crystalline complexes are powerful tools for the design and developing of new generation of reusable smart materials. In this work, a unique photoreactive olefin-containing metal-organic coordination polymer [Ag2(2,3-ppe)2(1,3-bdc)]n (1) was prepared by the hydrothermal reaction between AgNO3, 1-(2-pyridyl)-2-(3-pyridyl)ethylene (2,3-ppe), and 1,3-benzenedicarboxylic acid (1,3-H2bdc). When exposed to sunlight, 1 can undergo single-crystal-to-single-crystal (SCSC) transformation to form [Ag2(dpdpcb)(1,3-bdc)]n (1a, dpdpcb = 1,3-di(2-pyridyl)-2,4-di(3-pyridyl)cyclobutane) through a [2 + 2] cycloaddition reaction. 1a can regenerate into 1 via the cycloreversion reaction based on the thermal effect of sunlight. Such a metal-organic complex exhibits interesting fluorescence switching behavior during the unprecedented fully solar-controlled reversible SCSC reaction, which makes it possible to be applied to the fields of optical memory storage and anti-counterfeiting.

Advances in enrichment and separation of cis-diol-containing compounds by porous organic frameworks

The design and synthesis of boronate affinity materials that show high efficiency, high selectivity, and high enrichment performance have gained significant attention. The principle of boronate affinity relies on the reversible covalent reactions, including the formation of stable five-membered or six-membered cyclic esters with cis-diol-containing compounds in alkaline aqueous media and dissociation of cyclic esters in an acidic surrounding to release cis-diol-containing compounds. Recently, various boronate affinity materials have been synthesized and utilized for selective enrichment of these compounds. Metal organic frameworks (MOFs) and covalent organic frameworks (COFs) have been widely used in chromatographic separation and sample pretreatment because of their adjustable pore size, high porosity, high specific surface area, tunable skeleton structure, and favorable chemical and thermal stability. To promote the enrichment selectivity of MOFs and COFs for cis-diol-containing compounds, boronic acid-functionalized MOFs and COFs with various structures and categories have been synthesized. This review summarizes more than 80 investigations into the categories, synthetic strategies, and applications of boronic acid-functionalized MOFs and COFs from the Science Citation Index. These synthesis methods include metal ligand-fragment co-assembly, post-synthetic modification, and bottom-up modification of boronic acid-functionalized porous materials. Although two modification strategies (post-synthetic and metal ligand-fragment co-assembly) have been introduced for the preparation of boronic acid-functionalized MOFs, the latter is more commonly adopted as it improves the enrichment selectivity and enrichment efficiency of MOFs. The common limitations of MOFs such as aggregation and aperture issues were also resolved. Boron affinity MOFs possessing favorable properties according to the characteristics of cis-diol-containing compounds, have also been synthesized. Furthermore, to facilitate enrichment and separation, many boronic acid-functionalized magnetic material MOFs have been developed for the enrichment and analysis of cis-diol-containing compounds. Additionally, the luminescent properties of Ln-MOFs have been used in combination with boronic acid affinity for the enrichment, separation, and subsequent detection of cis-diol-containing compounds. Post-synthetic modification and the bottom-up strategy are the primary methods for the preparation of boronic acid-functionalized COFs. Boronic acid-functionalized COFs are less investigated than boronic acid-functionalized MOFs, likely due to the greater complexity of COF synthesis. This work aims to summarize the research advances, synthesis ideas, and synthesis methods related to boric acid-functionalized porous organic frameworks, which will provide theoretical guidance and technical support for its applications while accelerating the commercialization of such organic frameworks.

The Nobel Prize in Chemistry 2022: Fulfilling Demanding Applications with Simple Reactions.

The Nobel Prize in Chemistry 2022 was awarded jointly to Carolyn R. Bertozzi, Morten Meldal, and K. Barry Sharpless "for the development of click chemistry and bioorthogonal chemistry". Such rapid, selective, and nontoxic covalent reactions that link two components together under benign conditions have led to a paradigm shift in basic research and practical applications.

An H2S-Regulated Artificial Nanochannel Fabricated by a Supramolecular Coordination Strategy.

Hydrogen sulfide (H2S), as the third gasotransmitter, has an important impact on physiological and pathological activities. Herein, we fabricated an artificial nanochannel with a conductance value of 2.01 nS via a supramolecular coordination strategy. Benefiting from the unique H2S-mediated covalent reaction, the nanochannel biosensor could change from ON to OFF states with the addition of H2S. Furthermore, this nanochannel directed the ion transport, showing a high rectification ratio as well as gating ratio. Subsequently, theoretical simulations were conducted to help to reveal the possible mechanism of the functionalized nanochannel. This study can provide insights for better understanding the process of H2S-regulated biological channels and fabricating gas gated nanofluids.

Investigation of the enhanced photoactivity of CdS/Bi2MoO6/MoSe2 and its application in antibody-free enzyme-assisted photoelectrochemical strategy for detection of N6-methyladenosine and FTO protein

N6-methyladenosine (m6A) is the most abundant and dynamic reversible modification of mRNA in eukaryotes discovered in the mid-1970s, which is widely involved in various physiological processes. Fat mass and obesity-associated protein (FTO protein) is not only a demethylase for m6A, but also a carcinogenic factor for many human cancers. Therefore, it is very important to build a simple and sensitive platform for simultaneous detection of m6A and FTO protein. To achieve this aim, a novel photoelectrochemical biosensor was constructed with the antibody-free detection strategy of DTT mediated –SH functionalization of m6A triggered by FTO protein catalyzed m6A oxidation. To achieve high detection sensitivity, CdS/Bi2MoO6/MoSe2 system with matched energy gap was employed as photoactive material. To achieve high detection selectivity, the –CH3 of m6A in the captured RNA sequence (m6A RNA) on the electrode surface was oxidized by FTO protein to form hydroxymethyl, followed with the covalent reaction of DTT with hydroxymethyl, making the labeling of m6A with –SH. Finally, a CdS nanoparticle was modified on the electrode through the specific covalent reaction between –SH and Cd, achieving the improvement of the photocurrent with the matched energy band. Under the optimal experimental conditions, the biosensor showed linear range from 0.001 to 50 nM and 0.0005–500 μg/L with the detection limit of 0.37 pM and 0.034 ng/L (S/N = 3) for m6A RNA and FTO protein, respectively. The applicability of the developed method was assessed by investigating the effect of entacapone on FTO protein activity.

Synthetic Mucin Gels with Self-Healing Properties Augment Lubricity and Inhibit HIV-1 and HSV-2 Transmission.

Mucus is a self-healing gel that lubricates the moist epithelium and provides protection against viruses by binding to viruses smaller than the gel's mesh size and removing them from the mucosal surface by active mucus turnover. As the primary nonaqueous components of mucus (≈0.2%-5%, wt/v), mucins are critical to this function because the dense arrangement of mucin glycans allows multivalence of binding. Following nature's example, bovine submaxillary mucins (BSMs) are assembled into "mucus-like" gels (5%, wt/v) by dynamic covalent crosslinking reactions. The gels exhibit transient liquefaction under high shear strain and immediate self-healing behavior. This study shows that these material properties are essential to provide lubricity. The gels efficiently reduce human immunodeficiency virus type 1 (HIV-1) and genital herpes virus type 2 (HSV-2) infectivity for various types of cells. In contrast, simple mucin solutions, which lack the structural makeup, inhibit HIV-1 significantly less and do not inhibit HSV-2. Mechanistically, the prophylaxis of HIV-1 infection by BSM gels is found to be that the gels trap HIV-1 by binding to the envelope glycoprotein gp120 and suppress cytokine production during viral exposure. Therefore, the authors believe the gels are promising for further development as personal lubricants that can limit viral transmission.