Topical formulation based on disease-specific nanoparticles for single-dose cure of psoriasis.

First-line treatments for mild to moderate psoriasis are typically topical formulations containing corticosteroids, however, the therapeutic efficacy of these formulations is compromised by limited penetration and skin retention. Even more challenging, off-target corticosteroids are known to adversely affect healthy skin, including induction of epidermal and dermal atrophy. Here, we report a nanoparticle-based topical formulation that cures psoriasis in a single dose, but leaves healthy skin intact. Specifically, we developed tris(hydroxymethyl)aminomethane-modified bioadhesive nanoparticles (Tris-BNPs) that exploit the high permeability characteristic of psoriasis to penetrate only psoriatic skin but not the healthy skin. Furthermore, as Tris-BNPs diffuse and penetrate into the epidermis, the Tris molecules slowly diffuse away, exposing the aldehyde groups of BNPs, which can bind to amine groups present within lesional skin, leading to long local retention of BNPs in lesions of psoriatic skin. The accumulated BNPs within lesions release corticosteroids over a ~ 3 day period to maintain local drug concentration above the therapeutic level. In addition to deeper penetration and longer retention compared with commercial psoriasis treatments, the topical applied Tris-BNPs were not affected by sweating, humidity, or active wiping due to their preferential accumulation between the stratum corneum and the basal cells of the epidermis. Overall, Tris-BNP as a topical formulation hold promise to overcome the limitations of current psoriasis treatment.

Ex Vivo Method to Simultaneously Evaluate Glucose Utilization, Uptake, and Production in Rat Liver.

A novel ex vivo method to simultaneously evaluate hepatic glucose utilization, uptake, and production was developed in rats. The right lateral lobe of the liver was perfused with Krebs-Henseleit bicarbonate buffer containing 5 mmol/L uniformly labeled 13C-glucose ([U-13C]-glucose). The whole glucose concentration in the perfusate was measured by colorimetric assay, and the concentrations of [U-12C]-glucose (natural isotope) or [U-13C]-glucose were estimated on the basis of the abundance ratio of [U-12C]-glucose or [U-13C]-glucose, which were measured by GC-MS. The difference in whole glucose and [U-13C]-glucose concentrations between the baseline and effluent perfusate represents hepatic glucose utilization and glucose uptake, respectively. The [U-12C]-glucose concentration in the effluent perfusate corresponds to hepatic glucose production. With this method, we clarified the precise mechanism that underlies the hepatic impairment of diabetic animals and pharmacological effects of anti-diabetic agents. Thus, this method is useful for the pathophysiological and pharmacological research of type 2 diabetes.

Electrochemical impedance spectroscopy reveals a new mechanism based on competitive binding between Tris and protein on a conductive biomimetic polydopamine surface.

A novel mechanism was developed to study the interaction of mussel inspired polydopamine surfaces with bovine serum albumin using cyclic voltammetry and electrochemical impedance spectroscopy supplemented with XPS, IR spectroscopy, UV spectroscopy and atomic force microscopy. The polydopamine surfaces reveal different mechanisms that give a new insight into understanding the interaction with BSA under the variable conditions used for PDA preparation and BSA adsorption. The study provides an in-depth analysis of the orientations and interactions of BSA with polydopamine surfaces. The protein interaction behavior changed significantly in different environments including different pH values and concentrations of buffer and it revealed a competitive binding mechanism of protein binding. The study provides an outlook for studying the interaction of protein foulants with PDA, which should be carried out in nucleophilic buffers, while the covalent binding or immobilization of biomolecules to PDA surfaces should be carried out in non-nucleophilic buffer for higher efficiency.

Crystal structures of human CK2α2 in new crystal forms arising from a subtle difference in salt concentration.

The catalytic subunits of protein kinase CK2 are classified into two subtypes: CK2α1 and CK2α2. CK2α1 is an attractive drug-discovery target for various diseases such as cancers and nephritis. CK2α2 is defined as an off-target of CK2α1 and is a potential target in the development of male contraceptive drugs. High-resolution crystal structures of both isozymes are likely to provide crucial clues for the design of selective inhibitors of CK2α1 and/or CK2α2. To date, several crystal structures of CK2α1 have been solved at high resolutions of beyond 1.5 Å. However, crystal structures of CK2α2 have barely achieved a low resolution of around 3 Šbecause of the formation of needle-shaped crystals. In this study, new crystal forms were exploited and one provided a crystal structure of CK2α2 at 1.89 Šresolution. This result, together with the structure of CK2α1, will assist in the development of highly selective inhibitors for both isozymes.

Relevance and bio-catalytic strategies for the kinetic resolution of ketoprofen towards dexketoprofen.

This review presents the most relevant investigations concerning the biocatalytic kinetic resolution of racemic ketoprofen to dexketoprofen for the last 22 years. The advantages related to the administration of the dex-enantiomer in terms of human health, the so called "chiral switch" in the pharmaceutical industry and the sustainability of biotransformations have been the driving forces to develop innovative technology to obtain dexketoprofen. In particular, the kinetic resolution of racemic ketoprofen through enantiomeric esterification and hydrolysis using lipases as biocatalysts are thoroughly revised and commented upon. In this context, the biocatalysts, acyl-acceptors (alcohols), reaction conditions, conversion, enantiomeric excess, and enantiomeric ratio among others are discussed. Moreover, the investigations concerning scaling up processes in order to obtain an optically pure enantiomer of the profen are presented. Finally, some guidelines about perspectives of the technology and research opportunities are given.

In vivo and in vitro depolymerizations of intracellular medium-chain-length poly-3-hydroxyalkanoates produced by Pseudomonas putida Bet001.

In vivo and in vitro depolymerizations of intracellular medium-chain-length poly-3-hydroxyalkanoates (mcl-PHA) in Pseudomonas putida Bet001 grown on lauric acid was studied. Both processes were studied under optimum conditions for mcl-PHA depolymerization viz. 0.2 M Tris-HCl buffer, pH 9, ionic strength (I) = 0.2 M at 30°C. For in vitro depolymerization studies, cell-free system was obtained from lysing bacterial cells suspension by ultrasonication at optimum conditions (frequency 37 kHz, 30% of power output, <25°C for 120 min). The comparison between in vivo and in vitro depolymerizations of intracellular mcl-PHA was made. In vitro depolymerization showed lower depolymerization rate but higher yield compared to in vivo depolymerization. The monomer liberation rate reflected the mol% distribution of the initial polymer subunit composition, and the resulting direct individual products of depolymerization were identical for both in vivo and in vitro processes. It points to exo-type reaction for both processes, and potential biological route to chiral molecules.

Application of a Biodegradable Polyesteramide Derived from L-Alanine as Novel Excipient for Controlled Release Matrix Tablets.

This pre-formulation study assays the capacity of the polyesteramide PADAS, poly (L-alanine-dodecanediol-L-alanine-sebacic), as an insoluble tablet excipient matrix for prolonged drug release. The flow properties of PADAS were suitable for tableting, and the compressibility of tablets containing exclusively PADAS was evaluated by ESEM observation of the microstructure. The tablets were resistant to crushing and non-friable and they did not undergo disintegration (typical features of an inert matrix). Tablets containing 33.33% sodium diclofenac (DF), ketoprofen (K) or dexketoprofen trometamol (DK-T) as a model drug, in addition with 66.67% of polymer, were formulated, and the absence of interactions between the components was confirmed by differential scanning calorimetry. Dissolution tests showed that PADAS retained DF and K and prolonged drug release, following a Higuchi kinetic. The tablets containing DK-T did not retain the drug sufficiently for prolonged release to be established. Tablets containing DK-T and 66.67, 83.33 or 91.67% PADAS, compressed at 44.48 or 88.96 kN, were elaborated to determine the influence of the polymer amount and of the compression force on DK-T release. Both parameters significantly delayed drug release, except when the proportion of polymer was 91.67%.

Double-blind, randomized, double-dummy clinical trial comparing the efficacy of ketorolac trometamol and naproxen for acute low back pain.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most common type of medication used in the treatment of acute pain. Ketorolac trometamol (KT) is a nonnarcotic, peripherally acting nonsteroidal anti-inflammatory drug with analgesic effects comparable to certain opioids. OBJECTIVE: The aim of this study was to compare the efficacy of KT and naproxen (NA) in the treatment of acute low back pain (LBP) of moderate-to-severe intensity. PATIENTS AND METHODS: In this 10-day, Phase III, randomized, double-blind, double-dummy, noninferiority trial, participants with acute LBP of moderate-to-severe intensity as determined through a visual analog scale (VAS) were randomly assigned in a 1:1 ratio to receive sublingual KT 10 mg three times daily or oral NA 250 mg three times daily. From the second to the fifth day of treatment, if patient had VAS >40 mm, increased dosage to four times per day was allowed. The primary end point was the reduction in LBP as measured by VAS. We also performed a post hoc superiority analysis. RESULTS: KT was not inferior to NA for the reduction in LBP over 5 days of use as measured by VAS scores (P=0.608 for equality of variance; P=0.321 for equality of means) and by the Roland-Morris Disability Questionnaire (P=0.180 for equality of variance test; P=0.446 for equality of means) using 95% confidence intervals. The percentage of participants with improved pain relief 60 minutes after receiving the first dose was higher in the KT group (24.2%) than in the NA group (6.5%; P=0.049). The most common adverse effects were heartburn, nausea, and vomiting. CONCLUSION: KT is not inferior in efficacy and delivers faster pain relief than NA.

Enantioselective oxidation of galactitol 1-phosphate by galactitol-1-phosphate 5-dehydrogenase from Escherichia coli.

Galactitol-1-phosphate 5-dehydrogenase (GPDH) is a polyol dehydrogenase that belongs to the medium-chain dehydrogenase/reductase (MDR) superfamily. It catalyses the Zn(2+)- and NAD(+)-dependent stereoselective dehydrogenation of L-galactitol 1-phosphate to D-tagatose 6-phosphate. Here, three crystal structures of GPDH from Escherichia coli are reported: that of the open state of GPDH with Zn(2+) in the catalytic site and those of the closed state in complex with the polyols Tris and glycerol, respectively. The closed state of GPDH reveals no bound cofactor, which is at variance with the conformational transition of the prototypical mammalian liver alcohol dehydrogenase. The main intersubunit-contacting interface within the GPDH homodimer presents a large internal cavity that probably facilitates the relative movement between the subunits. The substrate analogue glycerol bound within the active site partially mimics the catalytically relevant backbone of galactitol 1-phosphate. The glycerol binding mode reveals, for the first time in the polyol dehydrogenases, a pentacoordinated zinc ion in complex with a polyol and also a strong hydrogen bond between the primary hydroxyl group and the conserved Glu144, an interaction originally proposed more than thirty years ago that supports a catalytic role for this acidic residue.

Kinetic analysis of the weak affinity interaction between tris and lysozyme.

The biosensor based on total internal reflection imaging ellipsometry (TIRIE), regarded as an automotive real-time research approach for biomolecular interaction, is introduced to analyze the kinetic process of the weak interaction between tris and lysozyme. The experiment is performed by delivering lysozyme solution diluted to different concentrations to the biosensor substrate interface immobilized with tris. By applying pseudo-first-order interaction kinetics model, we are able to obtain the kinetic parameters from fitting experimental data. The calculated association rate constant and dissociation rate constant of tris and lysozyme interaction are in 10(-2) mol(-1) s(-1) and 10(3)s(-1) magnitude, respectively. To further improve TIRIE's ability for kinetically characterizing biomolecular interaction, a theoretical method to deduce associate rate constant before experiment is proposed.

Downregulation of TES by hypermethylation in glioblastoma reduces cell apoptosis and predicts poor clinical outcome.

BACKGROUND: Gliomas are the most common human brain tumors. Glioblastoma, also known as glioblastoma multiform (GBM), is the most aggressive, malignant, and lethal glioma. The investigation of prognostic and diagnostic molecular biomarkers in glioma patients to provide direction on clinical practice is urgent. Recent studies demonstrated that abnormal DNA methylation states play a key role in the pathogenesis of this kind of tumor. In this study, we want to identify a novel biomarker related to glioma initiation and find the role of the glioma-related gene. METHODS: We performed a methylation-specific microarray on the promoter region to identify methylation gene(s) that may affect outcome of GBM patients. Normal and GBM tissues were collected from Tiantan Hospital. Genomic DNA was extracted from these tissues and analyzed with a DNA promoter methylation microarray. Testis derived transcript (TES) protein expression was analyzed by immunohistochemistry in paraffin-embedded patient tissues. Western blotting was used to detect TES protein expression in the GBM cell line U251 with or without 5-aza-dC treatment. Cell apoptosis was evaluated by flow cytometry analysis using Annexin V/PI staining. RESULTS: We found that the TES promoter was hypermethylated in GBM compared to normal brain tissues under DNA promoter methylation microarray analysis. The GBM patients with TES hypermethylation had a short overall survival (P <0.05, log-rank test). Among GBM samples, reduced TES protein level was detected in 33 (89.2%) of 37 tumor tissues by immunohistochemical staining. Down regulation of TES was also correlated with worse patient outcome (P <0.05, log-rank test). Treatment on the GBM cell line U251 with 5-aza-dC can greatly increase TES expression, confirming the hypermethylation of TES promoter in GBM. Up-regulation of TES prompts U251 apoptosis significantly. This study demonstrated that both TES promoter hypermethylation and down-regulated protein expression significantly correlated with worse patient outcome. Treatment on the GBM cell line (U251) with 5-aza-dC can highly release TES expression resulting in significant apoptosis in these cells. CONCLUSIONS: Our findings suggest that the TES gene is a novel tumor suppressor gene and might represent a valuable prognostic marker for glioblastoma, indicating a potential target for future GBM therapy.

Use of hypometabolic TRIS extenders and high cooling rate refrigeration for cryopreservation of stallion sperm: presence and sensitivity of 5' AMP-activated protein kinase (AMPK).

This study evaluated the effect of the use of hypometabolic TRIS extenders in the presence or the absence of AMPK activators as well as the utilization of high cooling rates in the refrigeration step on the freezability of stallion sperm. Twelve ejaculates were cryopreserved using Botucrio® as a control extender and a basic TRIS extender (HM-0) separately supplemented with 10 mM metformin, 2mM 5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside (AICAR), 2 mM Adenosine monophosphate (AMP), 40 µM compound C AMPK inhibitor or 2 mM AMP+40 µM compound C. Our results showed that the utilization of a hypometabolic TRIS extender supplemented or not with AMP or metformin significantly improves stallion sperm freezability when compared with a commercial extender. Additionally, high cooling rates do not affect stallion sperm quality after cooling and post-thawing. Finally, stallion spermatozoa present several putative AMPK sperm isoforms that do not seem to respond to classical activators, but do respond to the Compound C inhibitor.

The role of hypertriglyceridemia in the development of atherosclerosis and endothelial dysfunction.

A hereditary postprandial hypertriglyceridemic rabbit (PHT rabbit) is a new dyslipidemic model showing remarkably high plasma triglycerides with only limited elevation of plasma total cholesterol. In PHT rabbits, plasma triglyceride was markedly elevated postprandially compared with healthy Japanese white (JW) rabbits. In physiological experiments, the ring preparation of the thoracic aorta was suspended in an organ bath filled with modified Krebs-Henseleit solution, and the developed tension was recorded. Endothelial function was evaluated by acetylcholine-induced vasorelaxation in each preparation with intact endothelium. The acetylcholine-induced endothelium-dependent relaxation was diminished in PHT compared with JW rabbits, suggesting endothelial dysfunction in PHT rabbits. Histological examination was carried out in adipose tissue, liver and aorta. They were fixed in formaldehyde and embedded in paraffin. The tissues were sliced (4 µm) and stained using hematoxylin-eosin solution. In the adipose tissue, the visceral fat accumulated, and the size of adipose cells was enlarged in PHT rabbits. The liver of the PHT rabbit was fatty and degenerated. In aorta, increased intimal thickness was observed, suggesting the progression of atherosclerosis in the PHT rabbit. This study suggests the important role of postprandial hypertriglyceridemia in atherosclerosis. By using PHT rabbits, the effects of hypertriglyceridemia on health and diseases could be evaluated precisely.

Enhanced transfection efficiency of poly(N,N-dimethylaminoethyl methacrylate)-based deposition transfection by combination with tris(hydroxymethyl)aminomethane.

We have developed a substrate-mediated transfection method called "deposition transfection technology" using a poly(N,N-dimethylaminoethylmethacrylate) (PDMAEMA) homopolymer with both thermoresponsive and cationic characteristics. In this study, we enhanced deposition transfection efficiency by using tris(hydroxymethyl)aminomethane (Tris buffer) as a pH adjuster for transfection solution composed of PDMAEMA and plasmid DNA (pDNA). PDMAEMA with a molecular weight of 9.7 × 10(4) g mol(-1) was synthesized by photoinduced radical polymerization. The pH of PDMAEMA solution was increased gradually in the range from 8 to 11 by the addition of Tris, and then the solubility of PDMAEMA was significantly decreased and the dissolution time was extended from 15 to 40 min at Tris/PDMAEMA ratio of 1 and higher. On the other hand, while the polyion complexes (polyplexes) were formed by mixing PDMAEMA with luciferase-encoding plasmid DNA even under an excess amount of Tris at Tris/PDMAEMA ratio of 8, the binding affinity between PDMAEMA and pDNA was decreased with increasing Tris at Tris/PDMAEMA ratio of 2 and higher. When HeLa cells, smooth muscle cells, and cardiac fibroblasts were transfected by the deposition method using polyplex solution containing various amounts of Tris, the transgene expression dramatically increased at a Tris/PDMAEMA ratio of 2 in all cell types, which were more than 150-fold in HeLa cells, 40-fold in smooth muscle cells, and 30-fold in cardiac fibroblasts compared to those in the Tris-free condition. In addition, the enhanced transgene expression by Tris was sustained for over 10 days post-transfection as well as that observed in Tris-free condition. Thus, deposition transfection efficiency can be dramatically enhanced by using Tris buffer as a pH adjuster for polyplex solution.

The structural domains of Pseudomonas aeruginosa phosphorylcholine phosphatase cooperate in substrate hydrolysis: 3D structure and enzymatic mechanism.

Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen. It colonizes different tissues by the utilization of diverse mechanisms. One of these may involve the breakdown of the host cell membrane through the sequential action of hemolytic phospholipase C and phosphorylcholine phosphatase (PchP). The action of hemolytic phospholipase C on phosphatidylcholine produces phosphorylcholine, which is hydrolyzed to choline (Cho) and inorganic phosphate by PchP. The available biochemical data on this enzyme demonstrate the involvement of two Cho-binding sites in the catalytic cycle and in enzyme regulation. The crystal structure of P. aeruginosa PchP has been determined. It folds into three structural domains. The first domain harbors all the residues involved in catalysis and is well conserved among the haloacid dehalogenase superfamily of proteins. The second domain is characteristic of PchP and is involved in the recognition of the Cho moiety of the substrate. The third domain stabilizes the relative position of the other two. Fortuitously, the crystal structure of PchP captures molecules of Bistris (2-[bis(2-hydroxyethyl)amino]-2-(hydroxymethyl)propane-1,3-diol) at the active site and at an additional site. This represents two catalytically relevant complexes with just one or two inhibitory Bistris molecules and provides the basis of the PchP function and regulation. Site-directed mutagenesis along with biochemical experiments corroborates the structural observations and demonstrates the interplay between different sites for Cho recognition and inhibition. The structural comparison of PchP with other phosphatases of the haloacid dehalogenase family provides a three-dimensional picture of the conserved catalytic cycle and the structural basis for the recognition of the diverse substrate molecules.

Evaluation of transepithelial stromal riboflavin absorption with enhanced riboflavin solution using spectrophotometry.

PURPOSE: To assess transepithelial stromal riboflavin absorption with an enhanced riboflavin solution (riboflavin 0.1%, 15% dextran T500 with trometamol (Tris-[hydroxymethyl]aminomethane) and sodium ethylenediaminetetraacetic acid by analyzing light-transmission properties of ex vivo rabbit corneas. SETTING: School of Optometry and Vision Sciences, Cardiff, Wales. DESIGN: Experimental study. METHODS: The enhanced riboflavin drops (Ricrolin TE) were applied every 3 minutes for 1 hour to 12 corneas (4 with intact epithelium, 4 with superficial scratches, 4 with 8.0 mm epithelial debridement). As a comparison, riboflavin drops without the enhancers (riboflavin 0.1%, 20% dextran T500) (normal riboflavin group) were applied to 12 corneas (4 with intact epithelium, 4 with superficial scratches, 4 with central epithelial debridement). A control group of 4 corneas with intact epithelium received balanced saline 0.9%. To assess enhanced riboflavin absorption, light-transmission spectra of the corneas were analyzed with a spectrophotometer. RESULTS: The spectra in corneas with intact epithelium in both riboflavin groups and in eyes with superficial scratches treated with normal riboflavin were similar to controls. Those with enhanced riboflavin and superficial scratches showed a homogeneous yellow discoloration of the cornea with a dip in light transmission between 400 and 490 nm, similar to that of the enhanced riboflavin solution. This was also seen, albeit of a greater magnitude, with complete epithelial removal, with eyes receiving enhanced riboflavin having a greater dip in transmission than eyes receiving normal riboflavin. CONCLUSIONS: Administration of enhanced riboflavin and superficial epithelial scratches allowed sufficient riboflavin stromal absorption to homogeneously alter the transmission spectra of rabbit corneas. This did not occur to the same extent with an intact epithelium or normal riboflavin with superficial scratches. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Influence of organic ions on DNA damage induced by 1 eV to 60 keV electrons.

We report the results of a study on the influence of organic salts on the induction of single strand breaks (SSBs) and double strand breaks (DSBs) in DNA by electrons of 1 eV to 60 keV. Plasmid DNA films are prepared with two different concentrations of organic salts, by varying the amount of the TE buffer (Tris-HCl and EDTA) in the films with ratio of 1:1 and 6:1 Tris ions to DNA nucleotide. The films are bombarded with electrons of 1, 10, 100, and 60 000 eV under vacuum. The damage to the 3197 base-pair plasmid is analyzed ex vacuo by agarose gel electrophoresis. The highest yields are reached at 100 eV and the lowest ones at 60 keV. The ratios of SSB to DSB are surprisingly low at 10 eV (∼4.3) at both salt concentrations, and comparable to the ratios measured with 100 eV electrons. At all characteristic electron energies, the yields of SSB and DSB are found to be higher for the DNA having the lowest salt concentration. However, the organic salts are more efficient at protecting DNA against the damage induced by 1 and 10 eV electrons. DNA damage and protection by organic ions are discussed in terms of mechanisms operative at each electron energy. It is suggested that these ions create additional electric fields within the groove of DNA, which modify the resonance parameter of 1 and 10 eV electrons, namely, by reducing the electron capture cross-section of basic DNA units and the lifetime of corresponding transient anions. An interstrand electron transfer mechanism is proposed to explain the low ratios for the yields of SSB to those of DSB produced by 10 eV electrons.

Evaluation of resveratrol oxidation in vitro and the crucial role of bicarbonate ions.

Polyphenols can oxidize in culture medium and produce artifacts in cell culture studies. However, the extent and mechanism of the oxidation of resveratrol, a polyphenol abundant in red wine, is unclear. We investigated the oxidation of resveratrol in vitro and the effects of various components of the culture medium on the degradation of resveratrol and the production of H(2)O(2). We found that 96% of resveratrol at a concentration of 200 microM was degraded in Base Modified Eagle Medium after 24 h of incubation at 37 degrees C, producing about 90 microM of H(2)O(2). Including sodium bicarbonate in the medium markedly stimulated resveratrol degradation and H(2)O(2) production. In sum, we found that bicarbonate ions played a crucial role in the oxidative degradation of resveratrol in vitro, and that the degradation of resveratrol can be avoided by withdrawing sodium bicarbonate from the medium. A mechanism for the oxidation of resveratrol is proposed.

Enzymatic degradation of κ-carrageenan in aqueous solution.

Enzymatic degradation of standard κ-carrageenan and the low-gelling hybrid κ-/µ-carrageenan were conducted using recombinant Pseudoalteromonas carrageenovora κ-carrageenase. The initial velocity of the enzyme was determined as a function of varying Tris or NaI concentrations and at constant 200 mM cosolutes concentration, adjusting NaI and Tris concentrations accordingly. In both cases, we observed strong inhibition of the enzyme with increasing amounts of iodide. The characterization of the κ- and κ-/µ-carrageenan ordering by optical rotation and the visualization of iodide binding on carrageenan by (127)I NMR revealed that inhibition was not caused by the disordered-ordered transition of carrageenan in NaI, but by iodide binding. These results were confirmed by analysis of the degradation products by gel permeation chromatography. Degradation of carrageenan in the disordered state led to a rapid decrease in molecular mass and the production of all possible neo-κ-carrabiose oligomers. In the ordered conformation, the degradation kinetics, the decrease of average molecular weight, and the chain population distribution of degradation products varied with iodide concentration. These observations were interpreted to be the result of increasing amounts of bound iodide on carrageenan helices that, in turn, impede enzyme catalysis. Based on these results, we propose a single-helix ordered conformation state for κ-carrageenan and reject the previously advocated double-helix model.