Substitution Of Carboxyl Group Research Articles

Molecular Properties of Carboxymethyl Chitosan and Its Complexes with Curcumin and Nicotinamide in Drug Delivery Applications: Molecular Docking and Molecular Dynamic Study

Carboxymethyl chitosan (CMCs) is a chitosan-derived compound usually used as a carrier matrix in drug delivery systems. There are three types of CMCs based on the location of carboxyl group substitution: N-CMCs, O-CMCs, and N,O-CMCs. The ability of CMCs as a carrier is related to the ability of CMCs to interact with drug molecules. In this work, curcumin and nicotinamide were used as drug models. The ability of CMCs to interact with drug models can be observed by the amount of interaction energy generated when CMCs interact with curcumin and nicotinamide. The purpose of this study is to determine the interaction energy generated when CMCs interact with curcumin and nicotinamide using molecular docking and molecular dynamic methods. The results showed the interaction energy between O-CMCs, N-CMCs, and N,O-CMCs (2 and 3 monomers) with curcumin and nicotinamide, respectively, ranged from -17.08 to -13.37 and -12.05 to -11.00 Kj/mol. Conformational changes in molecular dynamic simulations affect bond-free energy, RMSD, and potential energy complex values.

Effect of degree of substitution of carboxyl groups on cross-linking of carboxymethyl starch

Cross-linked carboxymethyl starch of different degrees of substitution-DS (DS, 0.14, and 0.49) was synthesized and investigated the effect of DS on cross-linking of starch derivatives. Native corn starch was first carboxymethylated in an alkaline condition of the alcoholic medium using sodium chloroacetate as a carboxymethylating agent. The aqueous Carboxy Methyl Starch (CMS) solutions (15 and 50%, w/w) were then irradiated by electron beam (EB) radiations at 1, 2, 3, 5, 10, 20, and 50 kGy dosages and underwent radiation cross-linking, resulting in a Cross-linked Carboxymethyl Starch (CCMS). The gel content to be estimated in the CCMS of different DS (0.14 and .049) with 50% (w/w) CMS was 1.3 and 19.2%. These are the maximum degrees of cross-link achieved with 50% (w/w) aqueous CMS irradiated at 5 and 2 kGy dosages. Our results showed that the cross-linking of CMS depends on the DS of carboxyl groups and the concentration of CMS. Maximum cross-linking observed with CMS of DS, 0.49, and 50% (w/w) concentration demonstrates that the increased DS and concentration of CMS are favorable for cross-linking of CMS.
 

Growth inhibition and deposition prevention of sulfide scales using dispersants

Although sulfide scales of FeS, PbS, and ZnS do not occur as frequently as carbonate and sulfate scales, it is difficult to remove them once they are formed and deposited. Effective prevention and remediation of sulfide scales have not been fully developed. For sulfide scales, the conventional threshold inhibition approach is not as effective as for carbonate and sulfate scales, presumably, due to strong ion pairs formation of FeS0 and fast precipitation kinetics of FeSs. Polyacrylamide (PAM), polyvinyl pyrrolidone (PVP), and carboxymethyl cellulose (CMC) were examined as dispersants for sulfide scales to prevent and mitigate sulfide scale deposition through controlling the particle sizes of FeS, PbS and ZnS. PAM, PVP, and CMC dispersed FeS particles more effectively at pH 6.7 than 5.0 and temperature 70 °C than 90 °C. PAM and CMC successfully dispersed FeS particles even in extremely high ionic strength (I) of 4.6 M, while, PVP, slightly less effective, up to I = 2.6 M. At pH 5.0 and 90 °C, CMC was able to disperse FeS particles up to I = 1.3 M and PVP up to I = 0.6 M. In contrast, PAM could not disperse FeS particles at all. When FeS particles were dispersed in the presence of polymeric dispersants, FeS particle sizes remained in nanometer ranges, from 100 to 600 nm. Our results demonstrated that CMC was the best dispersant for FeS particles among the three polymers we tested. For CMC, the larger molecular weight and the lower degree of substitution of carboxylic groups on cellulose, the more effective dispersant CMC became. PbS and ZnS were also well dispersed in the presence of CMC. Almost all fraction of PbS particles was smaller than 200 nm, while about 60% of ZnS particles were smaller than 200 nm. Results demonstrated that the promising treatment selection of CMC as a universal dispersant for sulfide scales.

The Carbazole Compounds Endowed with Phosphonic Anchoring Group for Sensitizer in Dye-Sensitized Solar Cells

The sensitizer dye contacts onto the TiO2 surface through an anchoring group in a Dye-Sensitized Solar Cells (DSSC). The thermal stability of the anchoring group and TiO2 binding contact is important to be considered in order to obtain the cell stability. Phosphonic acid is an anchoring group that has a good binding-contact thermal stability with TiO2 surface. In this research we investigated through the computational study the electronic properties of carbazole derivative compounds endowed with the phosphonic anchoring-groups (CP). A series of 10 CP derivatives was studied which has a different functional donor group. The electronic properties were investigated using the TD-DFT method with the CAM-B3LYP basis set. The substitution of carboxyl group with the phosphonic one showed the absorption spectrum to the blue shift (5-70 nm) which gave a less beneficial effect to the DSSC performance. The addition of donor functional group aniline into the CP (aniline-CP) could shift back the absorption spectrum to the red-shift. The DSSC parameter also has been calculated including the electron injection driving force ΔGinject and the open circuit votage (eVOC). Overall the aniline-CP has the best performance among the observed compounds which showed the highest ΔGinject (-0.84872 eV) and eVOC (2.763 V).

Antigen Delivery to Antigen-Presenting Cells for Adaptive Immune Response by Self-Assembled Anionic Polysaccharide Nanogel Vaccines.

Although current vaccine technology induces sufficient antibody responses to prophylactically ward off viral infections, an anticancer vaccine that directs the patient's immune system to directly fight extant malignant cells will require inducing Th1 and cytotoxic T lymphocyte responses in addition to antibody-mediated activities. Thus, new mechanisms are necessary to deliver antigen to cells in the lymphatic system that will induce these responses. To this end, we have developed a cholesterol-bearing pullulan (CHP) self-assembly nanogel of less than 100 nm, which we have now further modified to be anionic by carboxyl group substitution. Overall, the nanogel-protected antigens during transport to the lymphatic system and converting the vehicle to an anionic charge improved interactions with antigen-presenting cells. We further show that these modified nanogels are a more efficient system for delivering antigen to antigen-presenting cells, particularly langerin-expressing cells, and that this induced significant adaptive immunity. Therefore, we think that this technology could be used to improve anticancer immunotherapies.

Effect of PCEs with Different Functional Groups on the Performance of Cement Paste

The adsorption behaviors and dispersing properties of polycarboxylate superplasticizer (PCE) with different functional groups were systematically analyzed to reveal the theory and methods of modifying PCE molecular structures and regulating PCE performances. By substituting carboxylic groups with sulfonic groups, ester groups or acylamino groups, respectively, modified PCEs with different functional groups were synthesized. Results show that introducing low amount of ester groups or sulfonic groups into the PCE molecules has no negative effects on the fluidity of cement paste, while introducing acylamino groups into PCE molecules significantly weakens the fluidity of cement paste. At low amount (when the molar ratio of sodium methallyl sulfonate to TPEG is lower than 0.4), the rapid adsorption of sulfonic groups onto the cement particles contributes to the high dispersing performance of the sulfonic group modified PCEs. When the substitution ratio of acrylic acid by sulfonic acid is higher than 0.4, the viscosity and the yield stress of cement paste increases sharply. Redundant sulfonic groups lead to the excessive charge density of the PCE, which contributes to the inhomogeneous adsorption on the cement grains and hence results in the decline of the dispersing performance. Substitution of carboxylic group by acylamino group or ester group slightly changes the viscosity as well as the yield stress of cement paste. Introducing sulfonic group into PCE molecule improves the adsorption behavior of PCEs, while introducing ester group or acylamino group into PCE depresses the adsorption properties.

Influence of aromatic structure and substitution of carboxyl groups of aromatic acids on their sorption to biochars

In order to clarify the influence of aromatic structure and COOH substitution of aromatic acids on their sorption to biochars, benzoic acid (BA), phthalic acid (PA), hemimellitic acid (HA), 2-biphenylcarboxylic acid (2-BA), 1-naphthoic acid (1-NA) and naphthalene were selected as model sorbates. Batch experiments on sorption of them to wheat straw-derived biochars at 300 °C (WS300) and 700 °C (WS700) were conducted. Results showed that WS700 with higher specific surface area and pore volume had faster and higher sorption of aromatic acids than WS300. Sorption affinity of aromatic acids decreased with increasing number of aromatic rings (BA > 1-NA > 2-BA), and was weakened by COOH substitution (BA > PA > HA). This was likely due to the π-electron delocalization into additional ring, reduced contact area of nonplanar aromatic structure on biochar surfaces, size exclusion of larger molecules in smaller pores of biochars and decreased hydrophobicity of aromatic acids by COOH substitution that abated the sorption. Dissociation of COOH substitution of aromatic acids also weakened their sorption to biochars due to the lower hydrophobicity of anionic species, and electrostatic repulsion between anionic species and negatively charged surface of biochars.

1,5-bis[2-(dioxyphosphoryl)-4-ethylphenoxy]-3-oxapentane and its Analogs as Promising Organic Ligands for Copper(II) Binding s

The dissociation and complexation ability toward Cu(II) of acidic type phosphoryl-containing podands – tetrabasic 1,5-bis[2-(dioxyphosphoryl)-4-ethylphenoxy]-3-oxapentane (L1), dibasic – 1,5-bis[2-(ethoxyhydroxyphosphoryl)-4-ethylphenoxy]-pentane (L2) and also of their carboxylic analogue dibasic 1,5-bis[2-(oxycarbonylphenoxy)]-3-oxapentane (L3) were investigated by spectrophotometric, conductometric and potentiometric methods in water in the presence 5% of dimethyl formamide. Spectrophotometric and conductometric titration data provided evidence for formation of 1:1 (M:L) complexes. The dissociation constants were determined and species distribution diagrams for studied acids were obtained by potentiometric method. These data are of interest for the design of binary extragents and medicinal drugs based on the studied ligands. The stability constants of Cu(II) 1:1 (M:L) complexes were estimated. Analysis of the titration curves suggests that deprotonation forms of the studied ligands react with Cu2+. Substitution of carboxylic groups in acyclic polyesters by phosphonic results in increased stability of the copper(II) complexes

Design, synthesis and biological evaluation of potential antibacterial butyrolactones

Novel butyrolactone analogues were designed and synthesized based on the known lichen antibacterial compounds, lichesterinic acids (B-10 and B-11), by substituting different functional groups on the butyrolactone ring trying to enhance its activity. All synthesized butyrolactone analogues were evaluated for their in vitro antibacterial activity against Streptococcus gordonii. Among the derivatives, B-12 and B-13 had the lowest MIC of 9.38μg/mL where they have shown to be stronger bactericidals, by 2–3 times, than the reference antibiotic, doxycycline. These two compounds were then checked for their cytotoxicity against human gingival epithelial cell lines, Ca9–22, and macrophages, THP-1, by MTT and LDH assays which confirmed their safety against the tested cell lines. A preliminary study of the structure–activity relationships unveiled that the functional groups at the C4 position had an important influence on the antibacterial activity. An optimum length of the alkyl chain at the C5 position registered the best antibacterial inhibitory activity however as its length increased the bactericidal effect increased as well. This efficiency was attained by a carboxyl group substitution at the C4 position indicating the important dual role contributed by these two substituents which might be involved in their mechanism of action.

Thermoreversible hydrogels based on triblock copolymers of poly(ethylene glycol) and carboxyl functionalized poly(ε-caprolactone): The effect of carboxyl group substitution on the transition temperature and biocompatibility in plasma

In this study we report on the development, characterization and plasma protein interaction of novel thermoresponsive in situ hydrogels based on triblock copolymers of poly(ethylene glycol) (PEG) and poly(α-carboxyl-co-benzyl carboxylate)-ε-caprolactone (PCBCL) having two different degrees of carboxyl group substitution on the PCBCL block. Block copolymers were synthesized through ring-opening polymerization of α-benzyl carboxylate-ε-caprolactone by dihydroxy PEG, leading to the production of poly(α-benzyl carboxylate-ε-caprolactone)–PEG–poly(α-benzyl carboxylate-ε-caprolactone) (PBCL–PEG–PBCL). This was followed by partial debenzylation of PBCL blocks under controlled conditions, leading to the preparation of PCBCL–PEG–PCBCL triblock copolymers with 30 and 54mol.% carboxyl group substitution. Prepared PCBCL–PEG–PCBCL block copolymers have been shown to have a concentration-dependent sol to gel transition as a result of an increase in temperature above ∼29°C, as evidenced by the inverse flow method, differential scanning calorimetry and dynamic mechanical analysis. The sol–gel transition temperature/concentration and dynamic mechanical properties of the gel were found to be dependent on the level of carboxyl group substitution. Both hydrogels (30 and 54mol.% carboxyl group substitution) showed similar amounts of protein adsorption but striking differences in the profiles of the adsorbed proteome. Additionally, the two systems showed similarities in their clot formation kinetics but substantial differences in clot endpoints. The results show great promise for the above-mentioned thermoreversible in situ hydrogels as biocompatible materials for biomedical applications.

Carboxymethylcellulose adsorption on molybdenite: the effect of electrolyte composition on adsorption, bubble-surface collisions, and flotation.

The adsorption of carboxymethylcellulose polymers on molybdenite was studied using spectroscopic ellipsometry and atomic force microscopy imaging with two polymers of differing degrees of carboxyl group substitution and at three different electrolyte conditions: 1 × 10(-2) M KCl, 2.76 × 10(-2) M KCl, and simulated flotation process water of multicomponent electrolyte content, with an ionic strength close to 2.76 × 10(-2) M. A higher degree of carboxyl substitution in the adsorbing polymer resulted in adsorbed layers that were thinner and with more patchy coverage; increasing the ionic strength of the electrolyte resulted in increased polymer layer thickness and coverage. The use of simulated process water resulted in the largest layer thickness and coverage for both polymers. The effect of the adsorbed polymer layer on bubble-particle attachment was studied with single bubble-surface collision experiments recorded with high-speed video capture and image processing and also with single mineral molybdenite flotation tests. The carboxymethylcellulose polymer with a lower degree of substitution resulted in almost complete prevention of wetting film rupture at the molybdenite surface under all electrolyte conditions. The polymer with a higher degree of substitution prevented rupture only when adsorbed from simulated process water. Molecular kinetic theory was used to quantify the effect of the polymer on the dewetting dynamics for collisions that resulted in wetting film rupture. Flotation experiments confirmed that adsorbed polymer layer properties, through their effect on the dynamics of bubble-particle attachment, are critical to predicting the effectiveness of polymers used to prevent mineral recovery in flotation.

Synthesis and cycloxygenase inhibitory properties of new naphthalene-methylsulfonamido, naphthalene-methylsulfonyl and tetrahydronaphthalen-methylsulfonamido compounds

We synthesized a series of new naphthalene derivatives: naproxen- and 6-methoxy naphthalene acetic acid-like 1–5. In these compounds the carboxylic function, typical of the classical NSAIDs, was replaced by a methylsulfonamido (1, 2 and 6a–c) or methylsulfonyl (3–5) group present in some selective COX-2 inhibitors. We also synthesized compounds 7 and 8 in which the naphthalene portion was substituted by tetrahydronaphthalene ring. Some of the new compounds were assayed for their enzymatic inhibitory activity towards cycloxygenase enzymes. Compounds 4 and 6b, at a concentration of 10 µM exhibit percentage inhibition values of 65%, 50% and 29%, 87% towards COX-2 and COX-1, respectively. The substitution of carboxylic group with a mehylsulfonamido or a methylsulfonyl groups does not allow to direct the selectivity versus to cycloxygenase enzymes.

Sulfation pattern of citrus pectin and its carboxy-reduced derivatives: Influence on anticoagulant and antithrombotic effects

Citrus pectin (CP), a polysaccharide composed of [→4)-α-d-GalpA-(1→]n, was submitted to one or four carboxy-reduction cycles, resulting in CP-CR1 and CP-CR4, which had 40% and 2% of GalpA units, respectively. The polysaccharides were chemically sulfated and their anticoagulant and antithrombotic effects determined. Sulfated polysaccharides (CP-S, CP-CR1S and CP-CR4S) had different anticoagulant activities, doubling APTT at concentrations of 28.7, 13.2, and 4.9μg/ml respectively. CP-CR1S and CP-CR4S also showed antithrombotic activity in vivo with ED50 of 3.01 and 1.70mg/kg, respectively. Like heparin, they inhibited thrombin by a mechanism dependent on AT and HCII. Their hemorrhagic potential was also similar to that of heparin. According to methylation analysis, 91.1% and 50.2% of 6-O-position in CP-CR4S and CP-CR1S were sulfated, respectively. Therefore, substitution of carboxyl groups by sulfate esters in these polysaccharides increases the anticoagulant and antithrombotic effects.

A new class of organosilane-modified polycarboxylate superplasticizers with low sulfate sensitivity

It is well-established that a competitive adsorption exists between polycarboxylate superplasticizers (SP) and sulfate ions solubilized in the interstitial solution of cement paste, which may cause a loss of the dispersing properties. This has been explained by competitive weak ionic interactions between functional carboxyl groups and sulfate ions with cement grains. In this study, SPs including trialkoxysilane functional groups have been synthesized. Adsorption and dispersing properties of these SPs were evaluated in the presence of different concentrations of Na 2SO 4 added in aqueous solution. It appeared that a partial substitution of carboxyl groups by trialkoxysilane in the polymer makes them more resistant to sulfate ions. We suggested that the high adsorption capacity of these SPs results from the formation of strong bonds between hydroxysilane groups and calcium silicate hydrate phases. The improved compatibility of these new silylated SPs has been demonstrated through the formulation of two different concrete equivalent mortars.

Characterization of the thermo- and pH-responsive assembly of triblock copolymers based on poly(ethylene glycol) and functionalized poly(ε-caprolactone)

A series of novel triblock copolymers composed of poly(ethylene glycol) (PEG) and poly(ε-caprolactone)-bearing benzyl carboxylate on the α-carbon of ε-caprolatone were synthesized through ring opening polymerization of α-benzyl carboxylate-ε-caprolactone by dihydroxylated PEG. The debenzylation of the synthesized copolymer, i.e., poly(α-benzyl carboxylate-ε-caprolactone)- b-PEG- b-poly(α-benzyl-carboxylate-ε-caprolactone) (PBCL- b-PEG- b-PBCL), in the presence of hydrogen gas using different levels of catalyst, was carried out to achieve copolymers with various degrees of free α-carboxyl to α-benzyl-ε-carboxylate groups on the hydrophobic block. Incomplete reduction of PBCL led to the formation of poly(α-carboxyl-co-benzyl caboxylate-ε-caprolactone) PCBCL in the lateral blocks at 27%, 50% and 75% carboxyl group substitution. The molecular weight and polydispersity of the resultant copolymers were estimated by 1H NMR and MALDI-TOF. Synthesized triblock copolymers formed stable micelles at low concentrations (critical micellar concentrations (CMC) of 0.34–12.5 μg ml −1). Polymers containing carboxyl groups in their structure showed a pH-dependent increase in CMC. As the pH was raised from 4.0 to 9.0, CMC increased from 0.76 to 1.06 μg ml −1, for 27% debenzylated polymer, and from 1.30 to 2.20 μg ml −1, for 50% debenzylated polymers. In contrast, the CMC in polymers without carboxyl group was independent of pH (0.55 μg ml −1). Different changes in micellar size as a function of temperature was observed depending on the degree of debenzylation on the PCBCL block: polymers with 27% degree of debenzylation illustrated a rise in micelle size from ∼38 to 55 nm as the temperature increased above 29 °C, while polymers with 50% debenzylation showed a decrease in micelle size, from ∼52 to 38 nm, with increase in temperature. A similar trend was observed at pH 4.5, 7.0 and 9.0 for polymers containing carboxyl groups on their hydrophobic block. The temperature for the onset of size change and/or the extent of aggregate size change was found to be dependent on the pH of the medium and the polymer concentration. The results point to a potential for the formation of thermo- and pH-responsive micelles from triblock copolymers of PEG and carboxyl substituted caprolactone. The results also imply a potential for the 27% debenzylated PCBCL- b-PEG- b-PCBCL copolymers to form a biodegradable thermoreversible gel with a transition temperature a few degrees below 37 °C.

The influence of types of dual modified starches on the enzymatic hydrolysis in the continuous recycle membrane reactor

The aim of work was to study the influence of the degree of substitution of acetylated oxidized starch (E-1451) on the process of enzymatic hydrolysis in a continuous recycle membrane reactor (CRMR). Three kinds of E-1451 starch preparations with different degrees of carboxyl group substitution (0.04, 0.11 and 0.5%) and with different degrees of acetylation: 0.5% and 2.5% (3%) were examined. The waxy corn modified starch was also investigated. Hydrolyses were performed in the CRMR equipped with an ultrafiltration module containing a ceramic membrane of tubular configuration. The membranes used were characterised by the following parameters: a length of 0.3 m, external diameter of 10 mm, three channels and a molecular weight cut-off of 50, 15 or 8 kDa. During the process the UF module was working in three variants: with a membrane of 15 kDa or a set of two membranes: 50/15 kDa and 15/8 kDa. The hydrolysis process was performed over a period of 150 min at a temperature of 60°C, at the transmembrane pressure of 0.5 MPa and with a 0.3 ml of enzyme preparation BAN 480 L per 1 kg of dry starch. It was stated that the efficiency of the separation process as well as the effectiveness of hydrolysis process was affected by the type of modification and the degree of substitution of starch.

Effect of introduced charge in cellulose gels on surface interactions and the adsorption of highly charged cationic polyelectrolytes

The interaction between cellulose surfaces in aqueous solution has been measured using colloidal probe microscopy. Cellulose thin films with varying charge through carboxyl group substitution were used in this study with the surface forces fit to DLVO theory. It was found that the surface potential increased, as expected, with increasing carboxyl substitution. Furthermore, for a given degree of substitution, the surface potential increased as a function of increasing pH. At low pH, the surface forces interaction were attractive and could be fit to the non-retarded Hamaker equation using a constant of 3 x 10(-21) J. At pH greater than 5, the force interactions were monotonically repulsive, regardless of the ionic strength of the solution for all charge densities of the cellulose thin films. The adsorption of polyDADMAC to these charged cellulose films was also investigated using the quartz crystal microbalance. It was found that for the low charge film, a low surface excess of PDADMAC was sensed and that the adsorbed conformation was essentially flat. However for the higher charged cellulose film, a spontaneous de-swelling was observed resulting in no possibility of quantitatively determining the sensed mass using QCM.

ChemInform Abstract: First Example of Memory of Chirality in Carbenium Ion Chemistry.

The non-Kolbe reaction of N-benzoyloxazolidine derivatives 6 derived from l-serine gave optically active N,O-acetals 7 when graphite was used as an anode material. This reaction represents the first example of “memory of chirality” in carbenium ion chemistry. The material used for the anode was critical for the memory of chirality. The substitution of carboxyl group with methoxyl group was found to proceed with an inversion mechanism.

First Example of Memory of Chirality in Carbenium Ion Chemistry

The non-Kolbe reaction of N-benzoyloxazolidine derivatives 6 derived from L-serine gave optically active N,O-acetals 7 when graphite was used as an anode material. This reaction represents the first example of "memory of chirality" in carbenium ion chemistry. The material used for the anode was critical for the memory of chirality. The substitution of carboxyl group with methoxyl group was found to proceed with an inversion mechanism.

Human Immune Response to Cationized Proteins: I. Characterization of the in Vitro Response to Cationized Diphteria Toxoid

Cationization of proteins, i.e., increasing net positive charge by the substitution of carboxyl groups with positively charged residues, has been reported to enhance protein immunogenicity in animal model systems. In the present study, we have investigated the effect of cationization on the in vitro cell-mediated immune response of human mononuclear cells to diphtheria toxoid. A series of cationized DT preparations were generated by covalent modification with ethylene-diamine, with pIs ranging from 4.6 to ≥9.3, and tested for their ability to induce proliferation of normal human peripheral blood mononuclear cells. Cationized DT (cDT) was found to induce an antigen-specific, augmented proliferative response, relative to native antigen, which was directly proportional to the degree of cationization. Further characterization of the response to cDT demonstrated that (1) proliferative responses could be detected considerably earlier, and typically at much lower antigen concentrations, than the response to native DT; (2) the response was dependent on HLA-DR: (3) production of a number of cytokines, sp. IL-1β, IL-2, and IFN-γ was also elevated in cDT-stimulated cultures; and (4) the enhanced proliferative response to cDT could be attributed to CD4 + helper T cells. These results demonstrate that cationization of proteins enhances the ability to generate a cell-mediated immune response in humans and suggest that cationization may have utility in the design of more effective carrier proteins for human vaccines.