Overlooked Iodo-Disinfection Byproduct Formation When Cooking Pasta with Iodized Table Salt.

Iodized table salt provides iodide that is essential for health. However, during cooking, we found that chloramine residuals in tap water can react with iodide in table salt and organic matter in pasta to form iodinated disinfection byproducts (I-DBPs). While naturally occurring iodide in source waters is known to react with chloramine and dissolved organic carbon (e.g., humic acid) during the treatment of drinking water, this is the first study to investigate I-DBP formation from cooking real food with iodized table salt and chloraminated tap water. Matrix effects from the pasta posed an analytical challenge, necessitating the development of a new method for sensitive and reproducible measurements. The optimized method utilized sample cleanup with Captiva EMR-Lipid sorbent, extraction with ethyl acetate, standard addition calibration, and analysis using gas chromatography (GC)-mass spectrometry (MS)/MS. Using this method, seven I-DBPs, including six iodo-trihalomethanes (I-THMs) and iodoacetonitrile, were detected when iodized table salt was used to cook pasta, while no I-DBPs were formed with Kosher or Himalayan salts. Total I-THM levels of 11.1 ng/g in pasta combined with cooking water were measured, with triiodomethane and chlorodiiodomethane dominant, at 6.7 and 1.3 ng/g, respectively. Calculated cytotoxicity and genotoxicity of I-THMs for the pasta with cooking water were 126- and 18-fold, respectively, compared to the corresponding chloraminated tap water. However, when the cooked pasta was separated (strained) from the pasta water, chlorodiiodomethane was the dominant I-THM, and lower levels of total I-THMs (retaining 30% of the I-THMs) and calculated toxicity were observed. This study highlights an overlooked source of exposure to toxic I-DBPs. At the same time, the formation of I-DBPs can be avoided by boiling the pasta without a lid and adding iodized salt after cooking.

Minimization of image lag in polycrystalline mercuric iodide converters through incorporation of Frisch grid structures for digital breast tomosynthesis.

Objective. Polycrystalline mercuric iodide photoconductive converters fabricated using particle-in-binder techniques (PIB HgI2) provide significantly more detected charge per x-ray interaction than from a-Se and CsI:Tl converters commonly used with active matrix flat-panel imagers (AMFPIs). This enhanced sensitivity makes PIB HgI2an interesting candidate for applications involving low x-ray exposures-since the relatively high levels of additive electronic noise exhibited by AMFPIs incorporating a-Se and CsI:Tl reduce detective quantum efficiency (DQE) performance under such conditions. A theoretical study is reported on an approach for addressing a major challenge impeding practical use of PIB HgI2converters-the high lag exhibited by the material (over 10%) which would lead to undesirable image artifacts in applications involving acquisition of consecutive images such as digital breast tomosynthesis.Approach. Charge transport modeling accounting for the trapping and release of holes (thought to be the primary contributor to lag) was used to examine signal properties, including lag, of pillar-supported Frisch grids embedded in the photoconductor for 100µm pitch AMFPI pixels. Performance was examined as a function of electrode voltage, grid pitch (center-to-center distance between neighboring grid wires) and the ratio of grid wire width to grid pitch.Main results. Optimum grid designs maximizing suppression of signal generated by hole transport, without significantly affecting the total signal due to electron and hole transport, were identified and MTF was determined. For the most favorable designs, additional modeling was used to determine DQE. The results indicate that, through judicious choice of grid design and operational conditions, first frame lag can be significantly reduced to below 1%-less than the low levels exhibited by a-Se. DQE performance is shown to be largely maintained as exposure decreases-which should help to maintain good image quality.Significance. Substantial reduction of lag in PIB HgI2converters via incorporation of Frisch grids has been demonstrated through modeling.

Enantioselective Reductive N-Cyclization-Alkylation Reaction of Alkene-Tethered Oxime Esters and Alkyl Iodides by Nickel Catalysis.

Asymmetric cross-electrophile difunctionalization of tethered alkenes has become a powerful tool for the production of chiral cyclic scaffolds; however, the current studies all focus on carbocyclization reactions. Herein, we report an N-cyclization-alkylation reaction and thus showcase the potential of heterocyclization for accessing new enantioenriched cyclic architectures. This work establishes a new approach for enantioselective aza-Heck cyclization/cross-coupling sequence, which remains a long-standing unsolved challenge for the synthetic community. The reaction proceeds with primary, secondary, and a few tertiary alkyl iodides, and the use of newly defined ligands gave highly enantioenriched pyrrolines with improved molecular diversity under mild conditions. The presence of imine functionality allows for further structural variations.

Photochromic immunoassay for tumor marker detection based on ZnO/AgI nanophotocatalyst.

A photochromic immunoassay was built for tumor marker detection based on ZnO/AgI nanophotocatalyst. Frist, ZnO/AgI nanoparticles were synthesized and characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray powder diffraction (XRD), and Fourier transform infrared spectrometry (FTIR). The color development is caused by tetramethyl benzidine (TMB) solution oxidated by ZnO/AgI nanomaterials. The electron transitions in ZnO/AgI nanomaterials are driven by visible light irradiation, generating photogenerated hole and oxidizing TMB to blue solution. Appropriate band width between ZnO and AgI promotes separation of photogenerated electrons and holes and enhances oxidation efficiency. A sandwich-type immunoassay was constructed based on ZnO/AgI nanomaterial as labels. The absorbance at 650 nm of reaction solution is positively correlated with antigen concentration. The developed immunoassay showed good performance for carcinoma embryonic antigen (CEA) detection in the range 0.1-7.0 ng/mL with a detection limit of 65 pg/mL. The photochromic immunoassay also exhibited preferable selectivity, repeatability, and stability. A novel colorimetric immunoassay was constructed based on ZnO/AgI photocatalyst. ZnO/AgI nanomaterials occur electron transitions under visible light irradiation and generate photogenerated hole, which can oxidize TMB to blue solution. Carcinoembryonic antigen in sample was detected sensitively due to the high catalytic efficiency of ZnO/AgI nanomaterials.

Design and construction of IR780- and EGCG-based and mitochondrial targeting nanoparticles and their application in tumor chemo-phototherapy.

An integration combination of phototherapy and chemotherapy to treat carcinoma, solving the inner limitation of individual-modal chemical agent-based therapy or phototherapy, emerges to be a strategy with high prospects for achieving synergistic curative effects. The dye IR780-iodide (IR780) close to infrared radiation is a phototherapy agent with high prospects. However, it is limited in its clinical applications due to poor solubility in water. While epigallocatechin-3-gallate (EGCG), naturally resourced green tea polyphenol, has been extensively proven with intrinsic antitumor activity, but it is largely restricted by its low bioavailability in vivo. Hence, novel multiple-function nanoparticles comprising hyaluronic acid (HA) and IR780 were proposed to deliver EGCG, defined as EGCG@THSI nano-scale particles (EGCG@THSI NPs), thereby rapidly solving limitations of EGCG and IR780. Amphiphilic nano-scale carrier was prepared by triphenylphosphine (TPP), hyaluronic acid (HA), cystamine, and IR780, termed as TPP-HA-SS-IR780, and EGCG was loaded into the amphiphilic copolymer by self-assembly. TPP-HA-SS-IR780 endowed the as-synthesized EGCG@THSI NPs with excellent TPP-mediated mitochondrial-targeted and glutathione-triggered rapid drug release properties. As impacted by the integration of phototherapy and chemotherapy, the EGCG@THSI NPs under NIR laser irradiation showed a prominent anti-tumor effect. Taken together, this study presented a multiple-function nano-scale carrier platform with high prospects in improving the therapeutic efficacy of anti-carcinoma drugs.

Iodide Analogs of Arsenoplatins-Potential Drug Candidates for Triple Negative Breast Cancers.

Patients with triple negative breast cancers (TNBCs)-highly aggressive tumors that do not express estrogen, progesterone, and human epidermal growth factor 2 receptors-have limited treatment options. Fewer than 30% of women with metastatic TNBC survive five years after their diagnosis, with a mortality rate within three months after a recurrence of 75%. Although TNBCs show a higher response to platinum therapy compared to other breast cancers, drug resistance remains a major obstacle; thus, platinum drugs with novel mechanisms are urgently needed. Arsenoplatins (APs) represent a novel class of anticancer agents designed to contain the pharmacophores of the two FDA approved drugs cisplatin and arsenic trioxide (As2O3) as one molecular entity. Here, we present the syntheses, crystal structures, DFT calculations, and antiproliferative activity of iodide analogs of AP-1 and AP-2, i.e., AP-5 and AP-4, respectively. Antiproliferative studies in TNBC cell lines reveal that all AP family members are more potent than cisplatin and As2O3 alone. DFT calculations demonstrate there is a low energy barrier for hydrolysis of the platinum-halide bonds in arsenoplatins, possibly contributing to their higher cytotoxicities compared to cisplatin.

Toward molecular imaging using spectral photon-counting computed tomography?

Molecular imaging is a valuable tool in drug discovery and development, early screening and diagnosis of diseases, and therapy assessment among others. Although many different imaging modalities are in use today, molecular imaging with computed tomography (CT) is still challenging owing to its low sensitivity and soft tissue contrast compared with other modalities. Recent technical advances, particularly the introduction of spectral photon-counting detectors, might allow overcoming these challenges. Herein, the fundamentals and recent advances in CT relevant to molecular imaging are reviewed and potential future preclinical and clinical applications are highlighted. The review concludes with a discussion of potential future advancements of CT for molecular imaging.

Role of various screening techniques in detecting preinvasive lesions of the cervix among symptomatic women and women having unhealthy cervix.

INTRODUCTION: Cervical cancer which is preventable, occurs due to humanpapiloma virus infection and results in a preinvasive condition called cervical intraepithelial neoplasm (CIN) before the development of cancer. Majority of the patients with CIN or early stage of cervical cancer present with symptoms such as abnormal vaginal discharge or bleeding, and unhealthy looking cervix. Selectively screening these symptomatic patients, can detect more number of positive cases and also most effective screening technique for these selective patients can be advocated. MATERIALS AND METHODS: All married women between 21 and 65 years attending gynecology outpatient department of a tertiary care health center in Central India and having unhealthy cervix or abnormal vaginal discharge were included. All women were subjected to Pap smear, visual inspection under acetic acid (VIA), visual inspection under Lugol's iodine (VILI) and colposcopy. Biopsy was taken in all cases. Diagnostic value of each screening method was determined in terms of sensitivity, specificity, positive predictive value and negative predictive value. RESULTS: Out of 352 patients, around 20% of them were found to have abnormal cytology. The sensitivity and specificity of Pap smear was found to be 34% and 94%. But colposcopy has high sensitivity and low specificity, i.e., 99% and 31%, respectively. On the other hand the sensitivity and specificity of VIA and VILI are comparable i.e., 65% and 45% and 64% and 48% respectively. Pap smear shows high positive predictive value among all, i.e., 85% and colposcopy shows 58% for the same. CONCLUSION: Pap smear carries low sensitivity but high positive predictive value. As compared to Pap smear, VIA and VILI are more sensitive and are of low cost. Colposcopy can be considered as a preferred method of screening due to its extremely high sensitivity.

Kinetic and structural analysis of the inactivation of urease by mixed-ligand phosphine halide Ag(I) complexes.

Soft metal ions can inactivate urease, a Ni(II)-dependent enzyme whose hydrolytic activity has significant implications in agro-environmental science and human health. Kinetic and structural studies of the reaction of Canavalia ensiformis urease (JBU) and Sporosarcina pasteurii urease (SPU) with Ag(I) compounds of general formula [Ag(PEt3)X]4 (X = Cl, Br, I), and with the ionic species [Ag(PEt3)2]NO3, revealed the role of the Ag(I) ion and its ligands in modulating the metal-enzyme interaction. The activity of JBU is obliterated by the [Ag(PEt3)X]4 complexes, with IC50 values in the nanomolar range; the efficiency of the inhibition increases in the Cl- < Br- < I- order. The activity of JBU upon [Ag(PEt3)2]NO3 addition decreases to a plateau corresponding to ca. 60% of the original activity and decreases with time at a reduced rate. Synchrotron X-ray crystallography on single crystals obtained after the incubation of SPU with the Ag(I) complexes yielded high-resolution (1.63-1.97 Å) structures. The metal-protein adducts entail a dinuclear Ag(I) cluster bound to the conserved residues αCys322, αHis323, and αMet367, with a bridging cysteine thiolate atom, a weak Ag…Ag bond, and a quasi-linear Ag(I) coordination geometry. These observations suggest a mechanism that involves the initial substitution of the phosphine ligand, followed by a structural rearrangement to yield the dinuclear Ag(I) cluster. These findings indicate that urease, in addition to the active site dinuclear Ni(II) cluster, possesses a secondary metal binding site, located on the mobile flap domain, capable of recognizing pairs of soft metal ions and controlling catalysis.

Tunicamycin as a Novel Redifferentiation Agent in Radioiodine Therapy for Anaplastic Thyroid Cancer.

The silencing of thyroid-related genes presents difficulties in radioiodine therapy for anaplastic thyroid cancers (ATCs). Tunicamycin (TM), an N-linked glycosylation inhibitor, is an anticancer drug. Herein, we investigated TM-induced restoration of responsiveness to radioiodine therapy in radioiodine refractory ATCs. 125I uptake increased in TM-treated ATC cell lines, including BHT101 and CAL62, which was inhibited by KClO4, a sodium-iodide symporter (NIS) inhibitor. TM upregulated the mRNA expression of iodide-handling genes and the protein expression of NIS. TM blocked pERK1/2 phosphorylation in both cell lines, but AKT (protein kinase B) phosphorylation was only observed in CAL62 cells. The downregulation of glucose transporter 1 protein was confirmed in TM-treated cells, with a significant reduction in 18F-fluorodeoxyglucose (FDG) uptake. A significant reduction in colony-forming ability and marked tumor growth inhibition were observed in the combination group. TM was revealed to possess a novel function as a redifferentiation inducer in ATC as it induces the restoration of iodide-handling gene expression and radioiodine avidity, thereby facilitating effective radioiodine therapy.

Development and characterization of an all-in-one gamma probe with auto-peak detection for sentinel lymph node biopsy based on NEMA NU3-2004 standard.

BACKGROUND: A gamma probe is a handheld device used for intraoperative interventions following interstitial injection of a radiotracer to locate regional lymph nodes through the external detection of radiation. This work reports on the design and performance evaluation of a novel fully integrated gamma probe (GammaPen), recently developed by our group. MATERIALS AND METHODS: GammaPen is an all-in-one pocket gamma probe with low weight and adequate dimensions, consisting of a detector, a control unit and output all together. The detector module consists of a cylindrical Thallium-activated Cesium Iodide [CsI (Tl)] crystal optically coupled to a Silicon photomultiplier (SiPM), shielded using Tungsten housing on side and back faces. The electronics of the probe consists of two small boards to handle signal processing and analog peak detection tasks. A number of parameters, including probe sensitivity in air/water, spatial resolution in air/water, angular resolution in air/water, and side and back shielding effectiveness, were measured to evaluate the performance of the probe based on NEMA NU3-2004 standards. RESULTS: The sensitivity of the probe in air at distances of 10, 30, and 50 mm is 18784, 3500, and 1575 cps/MBq. The sensitivity in scattering medium was also measured at distances of 10, 30, and 50 mm as 17,680, 3050, and 1104 cps/MBq. The spatial and angular resolutions in scattering medium were 47 mm and 87 degree at 30 mm distance from the probe, while they were 40 mm and 77 degree in air. The detector shielding effectiveness and leakage sensitivity are 99.91% and 0.09%, respectively. CONCLUSION: The performance characterization showed that GammaPen can be used effectively for sentinel lymph node localization. The probe was successfully used in several surgical interventions by an experienced surgeon confirming its suitability in a clinical setting.

Iodido equatorial ligands influence on the mechanism of action of Pt(IV) and Pt(II) anti-cancer complexes: A DFT computational study.

A detailed computational exploration of the most relevant steps of iodido Pt(IV) complexes reduction and Pt(II) drugs mechanism of action and eventual deactivation is presented here inspired by the recent findings on iodido Pt(II) complexes and surprising re-evaluation of their cytotoxic activity. Pt(II) and Pt(IV) model systems are investigated and compared with cisplatin and its Pt(IV) derivative. Both monodeprotonated ascorbic acid and l-cysteine are used as reducing agents in the inner-sphere reduction mechanism of Pt(IV) complexes. Aquation mechanism of iodido Pt(II) complexes, interaction with guanine and sulfur containing compounds and reaction with the model protein hen egg white lysozyme are explored, due to a detected different behavior with respect to classical platinum drugs. The outcomes of such exploration allow to shed light on the role that the increased soft character together with bridging and leaving abilities of iodide over chloride could play in determining the cytotoxic profile of iodido Pt drugs.

Construction of Cyclophane-Braced Peptide Macrocycles via Palladium-Catalyzed Picolinamide-Directed Intramolecular C(sp2)-H Arylation.

A versatile method for the construction of C(sp2)-linked cyclophane peptide macrocycles via Pd-catalyzed picolinamide-directed intramolecular arylation of aryl and alkenyl C-H bonds of amino acid side chains with aryl iodides is developed. This method provides simple and efficient access to a variety of cyclophane-braced structures from readily accessible linear peptide precursors.

Synthesis of Cyclophane-Braced Peptide Macrocycles via Palladium-Catalyzed Intramolecular C(sp3)-H Arylation of N-Methyl Alanine at C-Termini.

A method for the construction of cyclophane-braced peptide macrocycles via Pd-catalyzed aminoquinoline-directed intramolecular C(sp3)-H arylation with aryl iodides is developed. Unlike our previous AQ-directed exo-type intramolecular C-H arylation of long alkyl tails, this endo-type C-H cyclization reaction takes places on the ß-methyl group of N-methyl alanine at the C-termini of peptides. Unusual C-N cleavage side products of Ala were observed and attributed to intramolecular deprotonation-assisted α,ß-elimination of the palladacycle intermediate.

Design, Synthesis, and Dual Evaluation of Quinoline and Quinolinium Iodide Salt Derivatives as Potential Anticancer and Antibacterial Agents.

A series of novel quinoline and quinolinium iodide derivatives were designed and synthesized to discover potential anticancer and antibacterial agents. With regard to anticancer properties, in vitro cytotoxicities against three human cancer cell lines (A-549, HeLa and SGC-7901) were evaluated. The antibacterial properties against two strains, Escherichia coli (ATCC 29213) and Staphylococcus aureus (ATCC 8739), along with minimum inhibitory concentration (MIC) values were evaluated. The target alkyliodine substituted compounds exhibited significant antitumor and antibacterial activity, of which compound 8-((4-(benzyloxy)phenyl)amino)-7-(ethoxycarbonyl)-5-propyl-[1,3]dioxolo[4,5-g]quinolin-5-ium (12) was found to be the most potent derivative with IC50 values of 4.45±0.88, 4.74±0.42, 14.54±1.96, and 32.12±3.66 against A-549, HeLa, SGC-7901, and L-02 cells, respectively, stronger than the positive controls 5-FU and MTX. Furthermore, compound 12 had the most potent bacterial inhibitory activity. The MIC of this compound against both E. coli and S. aureus was 3.125 nmol ⋅ mL-1 , which was smaller than that against the reference agents amoxicillin and ciprofloxacin.

Infrared and 2-Dimensional Correlation Spectroscopy Study of the Effect of CH3NH3PbI3 and CH3NH3SnI3 Photovoltaic Perovskites on Eukaryotic Cells.

We studied the effect of the exposure of human A549 and SH-SY5Y cell lines to aqueous solutions of organic/inorganic halide perovskites CH3NH3PbI3 (MAPbI3) and CH3NH3SnI3 (MASnI3) at the molecular level by using Fourier transform infrared microspectroscopy. We monitored the infrared spectra of some cells over a few days following exposure to the metals and observed the spectroscopic changes dominated by the appearance of a strong band at 1627 cm-1. We used Infrared (IR) mapping to show that this change was associated with the cell itself or the cellular membrane. It is unclear whether the appearance of the 1627 cm-1 band and heavy metal exposure are related by a direct causal relationship. The spectroscopic response of exposure to MAPbI3 and MASnI3 was similar, indicating that it may arise from a general cellular response to stressful environmental conditions. We used 2D correlation spectroscopy (2DCOS) analysis to interpret spectroscopic changes. In a novel application of the method, we demonstrated the viability of 2DCOS for band assignment in spatially resolved spectra. We assigned the 1627 cm-1 band to the accumulation of an abundant amide or amine containing compound, while ruling out other hypotheses. We propose a few tentative assignments to specific biomolecules or classes of biomolecules, although additional biochemical characterization will be necessary to confirm such assignments.

Nucleophilic phenylation: a remarkable application of alkoxymethyltriphenylphosphonium salts.

A new application of α-alkoxymethylphosphonium salts in the nucleophilic phenylation of carbonyl compounds is demonstrated. Phenylation of aldehydes, ketones and acyl halides were studied by employing α-alkoxymethyltriphenylphosphonium halides in the presence of lithium hydroxide. New application of α-alkoxymethyltriphenylphosphonium salts. Metal-free, mild and selective phenylation. Easy preparation and handling of the reagent.

Thyroid Peroxidase Activity is Inhibited by Phenolic Compounds-Impact of Interaction.

The aim of this study was to estimate the mode of thyroid peroxidase (TPO) inhibition by polyphenols: Chlorogenic acid, rosmarinic acid, quercetin, and rutin. All the tested polyphenols inhibited TPO; the IC50 values ranged from 0.004 mM to 1.44 mM (for rosmarinic acid and rutin, respectively). All these pure phytochemical substances exhibited different modes of TPO inhibition. Rutin and rosmarinic acid showed competitive, quercetin-uncompetitive and chlorogenic acid-noncompetitive inhibition effect on TPO. Homology modeling was used to gain insight into the 3D structure of TPO and molecular docking was applied to study the interactions of the inhibitors with their target at the molecular level. Moreover, the type and strength of mutual interactions between the inhibitors (expressed as the combination index, CI) were analyzed. Slight synergism, antagonism, and moderate antagonism were found in the case of the combined addition of the pure polyphenols. Rutin and quercetin as well as rutin and rosmarinic acid acted additively (CI = 0.096 and 1.06, respectively), while rutin and chlorogenic acid demonstrated slight synergism (CI = 0.88) and rosmarinic acid with quercetin and rosmarinic acid with chlorogenic acid showed moderate antagonism (CI = 1.45 and 1.25, respectively). The mixture of chlorogenic acid and quercetin demonstrated antagonism (CI = 1.79). All the polyphenols showed in vitro antiradical ability against 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid), ABTS. The highest ability (expressed as IC50) was exhibited by rosmarinic acid (0.12 mM) and the lowest value was ascribed to quercetin (0.45 mM).

Prevalence of precancerous cervical lesions in women attending Mezam Polyclinic Bamenda, Cameroon.

INTRODUCTION: Precancerous cervical lesion is significantly a health problem globally. Thus, screening targeting women between the ages of 17-60 is being undertaken in developing countries, including Cameroon. Over 50% (7.8 per 100,000) women die of cervical cancer every year. This study was to determine the prevalence of precancerous cervical lesion, the age demography and access the risk factor. METHODS: A hospital-based cross-sectional study was conducted from August 09th to October 17th 2017. A total of 60 women participated, and were screened for precancerous cervical lesion. Data were collected by using a questionnaire. Visual inspection with acetic acid and visual inspection with Lugol's iodine was applied for the screening. SPSS version 16.0 was used for data entry and analysis. Logistic regression analysis was fitted and odds ratios with 95% confidence intervals and p-values were computed to identify factors associated with precancerous cervical cancer lesion. RESULTS: Out of 60 study participants, 2(3.33%) were found to be positive for precancerous cervical cancer lesion. CONCLUSION: The prevalence of precancerous cervical lesion in women that consulted at the Mezam polyclinic is high.

Ketones from Nickel-Catalyzed Decarboxylative, Non-Symmetric Cross-Electrophile Coupling of Carboxylic Acid Esters.

Synthesis of the C-C bonds of ketones relies upon one high-availability reagent (carboxylic acids) and one low-availability reagent (organometallic reagents or alkyl iodides). We demonstrate here a ketone synthesis that couples two different carboxylic acid esters, N-hydroxyphthalimide esters and S-2-pyridyl thioesters, to form aryl alkyl and dialkyl ketones in high yields. The keys to this approach are the use of a nickel catalyst with an electron-poor bipyridine or terpyridine ligand, a THF/DMA mixed solvent system, and ZnCl2 to enhance the reactivity of the NHP ester. The resulting reaction can be used to form ketones that have previously been difficult to access, such as hindered tertiary/tertiary ketones with strained rings and ketones with α-heteroatoms. The conditions can be employed in the coupling of complex fragments, including a 20-mer peptide fragment analog of Exendin(9-39) on solid support.