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Considering the vast importance of peptide and protein interactions with inorganic surfaces, probing hydrogen bonding during their adsorption on metal oxide surfaces is a relevant task that could shed light on the essential features of their interplay. This work is devoted to studying the dipeptides' adsorption on anatase nanoparticles (ANs) in light and heavy water to reveal differences arising upon the change of the major hydrogen bonding carrier. Thermodynamic study of six native dipeptides' adsorption on ANs in both media shows a strong influence of the solvent on the Gibbs free energy and the effect of side-chain mobile protons on the entropy of the process. The adsorption is endothermic irrespective of the medium and is entropy-driven. Computer simulations of peptide adsorption in both media shows similarity in binding via an amino group and demonstrates structural features of protonated and deuterated peptides in obtained complexes. Calculated peptide- anatase nanoparticle (AN) descriptors indicate surface oxygens as points of peptide-nanoparticle contacts.

This paper presents an improved synthesis of 4,7-dibromobenzo[d][1,2,3]thiadiazole from commercially available reagents. According to quantum-mechanical calculations, benzo[d][1,2,3]thiadiazole (isoBTD) has higher values of ELUMO and energy band gap (Eg), which indicates high electron conductivity, occurring due to the high stability of the molecule in the excited state. We studied the cross-coupling reactions of this dibromide and found that the highest yields of π-spacer–acceptor–π-spacer type compounds were obtained by means of the Stille reaction. Therefore, 6 new structures of this type have been synthesized. A detailed study of the optical and electrochemical properties of the obtained π-spacer–acceptor–π-spacer type compounds in comparison with isomeric structures based on benzo[c][1,2,5]thiadiazole (BTD) showed a red shift of absorption maxima with lower absorptive and luminescent capacity. However, the addition of the 2,2′-bithiophene fragment as a π-spacer resulted in an unexpected increase of the extinction coefficient in the UV/vis spectra along with a blue shift of both absorption maxima for the isoBTD-based compound as compared to the BTD-based compound. Thus, a thorough selection of components in the designing of appropriate compounds with benzo[d][1,2,3]thiadiazole as an internal acceptor can lead to promising photovoltaic materials.

Dibromoderivatives of benzofused chalcogen-nitrogen heterocycles are important precursors in the synthesis of various photovoltaic materials. 4,7-Dibromobenzo[d][1,2,3]thiadiazole is a practically unexplored compound in this series. In this communication, it was shown that the nucleophilic substitution of 4,7-dibromobenzo[d][1,2,3]thiadiazole with morpholine gave selectively 4-substituted product—4-(7-bromobenzo[d][1,2,3]thiadiazol-4-yl)morpholine. The structure of the newly synthesized compound was established by means of elemental analysis, high resolution mass-spectrometry, 1H, 13C NMR, and IR spectroscopy, mass-spectrometry, and X-ray analysis.

A new synthetic pathway to four substituted imidazoles from readily available 2-((4-aryl(thienyl)-5H-1,2,3-dithiazol-5-ylidene)amino)phenols has been developed. Benzo[d]oxazol-2-yl(aryl(thienyl))methanimines were proved as key intermediates in their synthesis. The formation of an imidazole ring from two methanimine derivatives likely includes the opening of one benzoxazole ring followed by ring closure by intermolecular nucleophilic attack of the N-methanimine atom to a carbon atom of another methanimine.

Sirtuin 1 (SIRT1) is a class III histone deacetylase that plays significant roles in the regulation of lifespan, metabolism, memory, and circadian rhythms and in the mechanisms of many diseases. However, methods of monitoring the pharmacodynamics of SIRT1-targeted drugs are limited to blood sampling because of the invasive nature of biopsies. For the noninvasive monitoring of the spatial and temporal dynamics of SIRT1 expression–activity in vivo by PET–CT–MRI, we developed a novel substrate-type radiotracer, [18F]-2-fluorobenzoylaminohexanoicanilide (2-[18F]BzAHA). PET–CT–MRI studies in rats demonstrated increased accumulation of 2-[18F]BzAHA-derived radioactivity in the hypothalamus, hippocampus, nucleus accumbens, and locus coeruleus, consistent with autoradiographic and immunofluorescent (IMF) analyses of brain-tissue sections. Pretreatment with the SIRT1 specific inhibitor, EX-527 (5 mg/kg, ip), resulted in about a 20% reduction of 2-[18F]BzAHA-derived-radioactivity accumulation in these structures. I...

This paper presents an improved synthesis of 4,7-dibromobenzo[d][1,2,3]thiadiazole from commercially available reagents. According to quantum-mechanical calculations, benzo[d][1,2,3]thiadiazole (isoBTD) has higher values of ELUMO and energy band gap (Eg), which indicates high electron conductivity, occurring due to the high stability of the molecule in the excited state. We studied the cross-coupling reactions of this dibromide and found that the highest yields of π-spacer–acceptor–π-spacer type compounds were obtained by means of the Stille reaction. Therefore, 6 new structures of this type have been synthesized. A detailed study of the optical and electrochemical properties of the obtained π-spacer–acceptor–π-spacer type compounds in comparison with isomeric structures based on benzo[c][1,2,5]thiadiazole (BTD) showed a red shift of absorption maxima with lower absorptive and luminescent capacity. However, the addition of the 2,2′-bithiophene fragment as a π-spacer resulted in an unexpected increase of the extinction coefficient in the UV/vis spectra along with a blue shift of both absorption maxima for the isoBTD-based compound as compared to the BTD-based compound. Thus, a thorough selection of components in the designing of appropriate compounds with benzo[d][1,2,3]thiadiazole as an internal acceptor can lead to promising photovoltaic materials.

O.I. Bol’shakov1, bolshakovoi@susu.ru V.A. Potemkin1, potemkinva@susu.ru M.A. Grishina1, grishinama@susu.ru A.S. Galushko2, galas74@inbox.ru S.V. Merzlov1, bostonbruins.2011.6@gmail.com R.S. Morozov1, yanatulskoi@mail.ru A.O. Shchelokov1, artyom.shchelokov@yandex.ru V.V. Popov3, Popov.ioc@gmail.com 1 South Ural State University, Chelyabinsk, Russian Federation 2 Institute of Organic Chemistry of the Russian Academy of Sciences, Moscow, Russian Federation 3 Wayne State University, Detroit, MI, USA Большаков Олег Игоревич – кандидат химических наук, научный сотрудник Управления научной и инновационной деятельности, Южно-Уральский государственный университет. 454080, г. Челябинск, пр. им. В.И. Ленина, 76. E-mail: bolshakovoi@susu.ru Потемкин Владимир Александрович – научный сотрудник Управления научной и инновационной деятельности, Южно-Уральский государственный университет. 454080, г. Челябинск, пр. им. В.И. Ленина, 76. E-mail: potemkinva@susu.ru Гришина Мария Александровна – главный научный сотрудник Высшей медико- биологической школы, Южно-Уральский государственный университет. 454080, г. Челябинск, пр. им. В.И. Ленина, 76. E-mail: grishinama@susu.ru Галушко Алексей Сергеевич – аспирант лаборатории металлокомплексных и наноразмерных катализаторов (№ 30), Институт органической химии им. Н.Д. Зелинского, РАН. 119991, г. Москва, Ленинский пр. 47. E-mail: galas74@inbox.ru Мерзлов Сергей Владимирович – инженер кафедры экологии и природопользования, химический факультет, Южно-Уральский государственный университет. 454080, г. Челябинск, пр. им. В.И. Ленина, 76. E-mail: bostonbruins.2001.6@gmail.com Морозов Роман Сергеевич – аспирант кафедры экологии и природопользования, Южно- Уральский государственный университет. 454080, г. Челябинск, пр. им. В.И. Ленина, 76. E-mail: yanatulskoi@mail.ru Щелоков Артем Олегович – студент кафедры химической технологии, Южно-Уральский государственный университет. 454080, г. Челябинск, пр. им. В.И. Ленина, 76. E-mail: artyom.shchelokov@yandex.ru Попов Вадим Владимирович – постдокторант факультета биомедицинской инженерии, Университет Уэйна, Wayne State University, 42. W. Warren Ave. Detroit, MI 48202, MI, USA. E-mail: popov.ioc@gmail.com Affinity characteristics of biomolecules, such as peptides and proteins, towards inorganic surfaces in general and to titanium oxide in particular become crucial in biotechnology and bionanotechnology. Amino acids are often used as “model” bits of peptides or proteins for studying their properties in different environments, and/or developing functional surfaces. Despite the great demand for knowledge about amino acid interactions with metal oxide surface, studies on the issue lack in consistency and represent a fragmentary picture. This paper is an attempt to study amino acid adsorption on nanocrystalline anatase systematically at uniform conditions. Features of the L-alanine adsorption have been revealed and interpreted with quantum-chemical calculations. Особенности взаимодействия биомолекул, таких как протеины и пептиды с неорганическими поверхностями вообще и с оксидом титана в частности становятся ключевым фактором биотехнологии и бионанотехнологии. Аминокислоты часто используются в качестве модельных фрагментов пептидов и протеинов для изучения их свойств в различных средах и при изучении новых поверхностей. Несмотря на высокий запрос на фундаментальные представления о взаимодействии биомолекул с поверхностью оксида титана, знания в этой области представлены фрагментарно и не дают целостной картины. В этой статье проведена попытка изучения сорбции аминокислот на оксиде титана в унифицированных условиях. Сорбция L-аланина была интерпретирована квантово- механическим моделированием. The reported study was funded by RFBR according to the research project № 15-03-07834-a.

Four new D-A-&pi, A metal-free organic sensitizers for dye-sensitized solar cells (DSSCs), with [1,2,5]thiadiazolo[3,4-d]pyridazine as internal acceptor, thiophene unit as &pi, spacer and cyanoacrylate as anchoring electron acceptor, have been synthesized. The donor moiety was introduced into [1,2,5]thiadiazolo[3,4-d]pyridazine by nucleophilic aromatic substitution and Suzuki cross-coupling reactions, allowing design of D-A-&pi, A sensitizers with the donor attached to the internal heterocyclic acceptor not only by the carbon atom, as it is in a majority of DSSCs, but by the nitrogen atom also. Although low values of power conversion efficiency (PCE) were found, a few important consequences were identified: (i) poor PCE data can be attributed to high electron deficiency of the internal [1,2,5]thiadiazolo[3,4-d]pyridazine acceptor due to lower light harvesting by the dye, (ii) the manner in which the donor was attached to the internal acceptor (by carbon or nitrogen) did not play an essential role in the photovoltaic properties of the dyes, (iii) dyes based on the novel donor 2,3,4,4a,9,9a-hexahydro-1H-1,4-methanocarbazolyl and 9-(p-tolyl)-2,3,4,4a,9,9a-hexahydro-1H- carbazole moieties showed similar photovoltaic properties to dyes based on the well-known 4-(p-tolyl)-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indolyl building block, which opens the door for further optimization potential of new dye families.

Surface properties of the nanostructured materials are essential in attaining particular functionality, which is why there are a plethora of surface modification methods applied during or past the synthesis of nanoparticular substrates. Depending on the resulting content of the surface it could be heterophase forming modifications or pristine titania modifications. In this communication, we study a novel approach to pristine titania surface alteration by controlled chemisorption of the stable water-soluble titanium complex on the nanocrystalline anatase. Following on-air calcination for removal of organic residues converts chemisorbed complexes into oxide phase increments. Such an approach retains crystallinity and specific surface with simultaneous withdrawal of surface hydroxyl groups.

The most common and important method of agricultural products processing is drying. The quality of finished product, energy intensity and material intensity of the entire processing depend on the drying process. Drying the seeds of different crops is influenced by many factors: the structure, size, properties and condition. We studied the process of drying oil-bearing small-seeded crops taking rapeseeds as samples. Rapeseed is covered with a hard shell that prevents the release of moisture; in this case the seeds should be dried at low temperatures. High temperature causes rapeseeds to have low quality indicators. Analysis of the existing equipment has shown that nowadays there are no special systems for drying small-seeded crops, and the drying process is carried out on grain dryers which are characterized by large seeds losses, considerable energy costs and high temperatures. The main advantages of the developed infrared dryer of conveyor cascade type are the lack of hot zones, the uniform heating and the minimum percentage of seeds losses because of their blowing out and removal. In addition, the heat carriers used in the dryer of conveyor cascade type help to perform the drying process at the required wavelength, that can affect only the moisture in the seeds.

The 11a,12-dihydrobenzo[b]benzo[5,6][1,4]oxazino[2,3-e][1,4]oxazine heterocyclic system has been used in the construction of heteropropellanes, which attracted much attention not only on the possible modification of drugs, but also for novel materials with unusual and important physical properties. In this communication, the reaction of ethyl 2-(hydroxyimino)propanoate 1 with disulfur dichloride and o-aminophenol, which gave ethyl 11a,12-dihydrobenzo[b]benzo[5,6][1,4]oxazino[2,3-e][1,4]oxazine-5a(6H)-carboxylate in moderate yield, was described. The structure of the newly synthesized compound was established by means of elemental analysis, high resolution mass-spectrometry, 1H, 13C NMR and IR spectroscopy, mass-spectrometry and X-ray analysis.

The synthesis of [1,3]dithiolo[4,5-d]dithiazolium salts from readily available zinc chelate has been developed. Chlorination of 2-oxo and 2-(dicyanomethylene) (2-oxo-1,3-dithiole-4,5-diyl) diethanethioates with SO2Cl2 followed by condensation with Me3SiN3 produced 1,2,3-dithiazolium chlorides. The structure of 5-(dicyanomethylene)[1,3]dithiolo[4,5-d][1,3,2]dithiazol-1-ium tetrafluoroborate was confirmed by powder X-ray diffraction, and its chemical bonding pattern as well as charge transfer were studied within the QTAIM framework applied to the results of plane wave DFT periodic calculations. Reduction with triphenylantimony and electrochemical reduction of [1,3]dithiolo[4,5-d]dithiazolium salts by cyclic voltammetry, chronoamperometry, and microelectrolysis at a controlled potential on a platinum electrode in acetonitrile revealed the formation of [1,3]dithiolo[4,5-d]dithiazolyl radicals, which were characterized by EPR spectroscopy.

Efficient syntheses of O-acyl Tyr-peptides allow chemical long-range ligation (O-acyl to N-acyl transfer) via each of 12- to 19-membered cyclic transition states. The results represent the first examples of successful isopeptide ligations starting from O-acyl Tyr-peptides.

The possibility of controlling the physicochemical properties of suspensions and the electrical properties of filled latex composites containing dispersed ferroelectrics was examined. The use of ferroelectrics as fillers allows preparation of polymeric composites with high dielectric constant ɛ and low dielectric loss, used, e.g., for the development of dielectric functional layers of electroluminescence light sources.

Galectin-3 (Gal-3) is a carbohydrate binding protein that is overexpressed in several types of cancers, including pancreatic cancer, which makes it a good target for both imaging and therapeutic drug design. A ligand library specialized for 18F positron emission tomography (PET) has been investigated with molecular dynamics (MD) and free energy methods to determine the relative binding energies of various potential ligands. Our results suggest that traditional docking methods can give good results when complemented by molecular dynamics and free energy methods for these types of ligands. Available experimental binding affinities for a small number of the tested compounds show very good agreement with the calculated energies and provide the rational approach for design of Gal-3 ligands with even higher affinity.

A synthesis of thieno[2,3-d][1,3,2]dithiazolium salts from commercial tetrahydrothiophene has been developed. The reaction of thieno[2,3-f][1,2,3,4,5]pentathiepin with LiAlH4 in THF at −15 °C, after treatment with acetyl chloride, led to 2,3-(bisacetylthio)thiophene in high yield. Bis(acetylthio)thiophene reacted with sulfuryl chloride and then trimethylsilyl azide was added to afford a 1,3,2-dithiazolium chloride which was converted into a soluble tetrafluoroborate. Electrolytic reduction under controlled potential yielded a thieno[2,3-d][1,3,2]dithiazolyl radical which was characterized by EPR in frozen methylene dichloride.

The reaction temperature has a strong impact on the results of chlorination of 5,6-bis(tertbutylthio)[1,2,5]oxadiazolo[3,4-b]pyrazine that is readily prepared from 5,6dichloro[1,2,5]oxadiazolo[3,4-b]pyrazine and sodium tert-butylsulfide. Monoand bis(sulfenylchlorides) were selectively obtained in high yield and their structure was confirmed by the reaction with morpholine. Treatment of [1,2,5]oxadiazolo[3,4-b]pyrazine-5,6-disulfenyl dichloride with primary aliphatic amines and benzylamine afforded N-substituted [1,3,2]dithiazolo[4,5-b][1,2,5]oxadiazolo[3,4-e]pyrazines in moderate yields. Novel pentacyclic [1,2,5]oxadiazolo[3'',4'':5',6']pyrazino[2',3':5,6][1,2,4]thiadiazino[3,4-b][1,3]benzothiazole, whose structure was confirmed by X-ray diffraction, was obtained by the reaction of this disulfenyl dichloride with 2-aminobenzothiazole.

Data on the synthesis and reactions of 1,3,2-dithiazoles over the last 30 years are reviewed and classified.

The possibility of controlling the physicochemical and electric properties of conducting latex composites based on butadiene-acrylonitrile latex and carbon fillers, using data on the content of active centers on the filler surface and their distribution with respect to donor-acceptor properties, was examined. To make the fillers compatible with the latexes and prevent their coagulation, the fillers were modified with Leukanol.

Dihalogenated derivatives of [1,2,5]chalcogenadiazolo[3,4-d]pyridazines are of interest as precursors for both photovoltaic materials and biologically active compounds. In this communication, 4,7-dichloro[1,2,5]oxadiazolo[3,4-d]pyridazine 1-oxide was prepared via the reaction of 3,6-dichloro-5-nitropyridazin-4-amine with oxidizing agents; the best yield of the target compound was achieved in the reaction with (diacetoxyiodo)benzene in benzene by heating at reflux for two hours. The structure of the newly synthesized compound was established by means of 13C-NMR and IR spectroscopy, mass-spectrometry and elemental analysis.

Substituted ethanone oximes react with S2Cl2 and pyridine to give 1,2,3-dithiazolium chlorides. The treatment of these products with malonodinitrile in dichloromethane affords 4-substituted 5 H-1,2,3-dithiazol-5-ylidenes. The reaction of the latter compounds with n-butylamine unexpectedly yielded addition products at one of the nitrile groups, viz. substituted 1,2,3-dithiazol-5-ylideneethanimidamides.

Chemical ligations to form native peptides from N→N acyl migrations in Trp-containing peptides via 10- to 18-membered cyclic transition states are described. In this study, a statistical, predictive model that uses an extensive synthetic and computational approach to rationalize the chemical ligation is reported. N→N acyl migrations that form longer native peptides without the use of Cys/Ser/Tyr residues or an auxiliary group at the ligation site were achieved. The feasibility of these traceless chemical ligations is supported by the N-C bond distance in N-acyl isopeptides. The intramolecular nature of the chemical ligations is justified by using competitive experiments and theoretical calculations.

5-Oxo[1,3]dithiolo[4,5-d][1,3,2]dithiazol-1-ium chloride was converted into [(4-sulfanylidene-4H-1λ4,3,2-dithiazol-5-yl)sulfanyl]-formic acid esters and amides upon treatment with alcohols and amines, respectively; the structure of propyl [(4-sulfanylidene-4H-1λ4,3,2-dithiazol-5-yl)sulfanyl]formate was confirmed by X-ray diffraction.

The synthesis of 5-oxo[1,3]dithiolo[4,5- d ][1,3,2]dithiazol-1-ium chloride 1a from easily available zink chelate, TEA[Zn(DMIT) 2 ], has been developed; salt 1a has been converted to the first representative of [1,3]dithiolo[4,5- d ]dithiazolyl radical, which was identified by EPR and CV data.

Histone deacetylases (HDACs) are involved in the pathogenesis of cancer through modulation of the expression of various genes involved in cellular proliferation, migration, angiogenesis and apoptosis. HDAC class IIa enzymes interact with tumor suppressor proteins including HIF-1a, GATA-1, and PLZF-RARa. Given the importance of HDACs class IIa in epigenetic regulation of cancer development, progression, and maintenance, there is a pressing need for non-invasive imaging approaches for monitoring the expression-activity of HDACs in vivo. To address this need, our laboratory has developed 6-(tri-fluoroacetamido)-1-hexanoicanilide (18F-TFAHA) for imaging HDAC class IIa enzymes. Previous studies show that 18F-TFAHA is enzymatically cleaved specifically by HDAC class IIa, predominantly by HDACs 4 and 5. To quantitatively visualize the expression-activity of HDACs 4 and 5 in brain gliomas, immunocompromised rats (NTac:NIH-Foxn1rnu, Taconic Biosciences, NY) were implanted intracerebrally (i.c.) with U87-tdRluc cells (4×105 cells in 20 uL), that have been lentivirally-transfected to express GFP-luciferase and tdTomato fluorescent protein fusion reporter genes. Bioluminescence images (BLI) of GBMs were obtained after administration of luciferin (10 μl/g i.p.) using an InVivo Xtreme system (Carestream, Toronto, Canada) at 7 and 14 days post U87-tdRluc cell implantation. Gross tumor morphology and progression was evaluated with T2 MRI on day 14 after tumor implantation using a CliniScan 7T MRI system (Bruker, UK). Following 15-20 days, the rats were administered with 18F-TFAHA (500 μCi/animal, i.v.) and imaged using microPET R4 and Inveon CT (Siemens, TN). After PET/CT imaging, the animals were sacrificed and their brains extracted for immunohistochemical (IHC) and quantitative autoradiographic (QAR) studies (Typhoon 7000, General Electric, CT). The 18F-TFAHA accumulation in regions of interest (ROI) at 20-30 minutes post i.v. administration and was quantified using Logan graphical analysis, which demonstrated a significant increase in 18F-TFAHA accumulation in tumors versus surrounding normal cortex and white matter (p Support: NIH RO1 DA030333-06, NCI CCGS Core Grant CA 016672, NIH RC2 DA028912-01, NIH P30 CA022453 Citation Format: Maxwell T. Laws, Robin E. Bonomi, Swatabdi Kamal, David Gelovani, Jeremy Llanguez, Vadim Popov, Xin Lu, Srinivasu Kallakuri, Thomas Mangner, Juri G. Gelovani. Molecular imaging of epigenetic regulation mediated by HDACs 4, 5 using PET/CT/MRI with 18F-TFAHA in a rat model of human glioma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3976.

Histone deacetylases (HDACs) play a pivotal role in epigenetic regulation through post translational modifications of histone core and other critical proteins in cellular pathways. The HDACs class III, sirtuins (SIRTs) 1-7, possess limited deacetylase activity. Each of these nicotinamide dinucleotide (NAD+) dependent enzymes have unique structures of catalytic sites that prefer larger lysine-modifying groups as substrates (i.e., glutaryl, succinyl, lipoyl, crotanyl, myristoyl). In particular, SIRT2 is a key regulator of nuclear H4K16 and cytoplasmic alpha-tubulin proteins, thereby acting as a mitotic exit regulator. From the literature, it is clear that SIRT2 plays a pivotal role in the regulation of cancers, so much so that it may switch between tumor suppressor and regulator at different stages of tumor progression. For this reason, SIRT2 has been identified as a possible target for cancer therapy but due to the pleiotropic roles of SIRT2 under normal and pathologic conditions, it is important to assess its activity during pharmacomodulation (i.e. activation or inhibition). Therefore, non-invasive PET imaging using SIRT2-specific substrate-type radiotracers may aid in the development of new SIRT2 inhibitors for therapy of cancer. Herein, we report novel synthesis of a focused library of compounds to assess the structure activity relationship (SAR) of SIRT2 with fluoroalkyl chain length varying between 3 and 16 carbons. The preliminary screening was performed with the tert-butyloxycarbonyl-lysine-aminomethylcoumarin (Boc-lys-AMC) backbone and Fluor-de-lys assay [1] to determine the chain length for optimal SIRT2 catalytic efficiency. Based on the analysis of Michealis-Menten kinetics of each substrate, myristoyl (14-carbon carboxylic acid) was cleaved most efficiently, followed by 12-fluorododecanoic and 10-fluorodecanoic acids (kcat/km = 4E-3, 1E-4, 8.9E-5 s-1uM-1, respectively). For in vivo PET imaging radiotracer development, we linked the 12-fluorododecanoic acid with the aminohexanoicanilide (AHA) backbone [2]. This compound was developed with a terminal bromine (precursor), iodine, fluorine, and F-18 (12-[18F]DDAHA). In vitro cellular uptake studies demonstrated a three-fold increase in accumulation of 12-[18F]DDAHA in U87 glioma cells as compared to MiaPaCa, MDA-MB-231, and MCF10A cell lines. The increased accumulation in the U87 glioma cells indicates that this compound may prove useful for detection of brain gliomas and for monitoring therapies with novel SIRT2 specific inhibitors. This insight into the catalytic activity of SIRT2 provides a basis for the development of a SIRT2-specific PET imaging agent to further probe the role of SIRT2-mediated epigenetic regulation in normal physiology and cancer. Citation Format: Robin E. Bonomi, Aleksandr Shavrin, Vadim Popov, Thomas Mangner, Juri G. Gelovani. Elucidating structure-activity relationships of SIRT2 and fluoroalkyl chain length to identify the lead candidate substrate radiotracer for PET imaging. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4234.

Mammography is the gold standard for breast cancer detection with sensitivity of 85%, which decreases to 68% in women with dense breasts and to 48% in women with extremely dense breasts, making cancer detection challenging. Additional methods for breast cancer screening have been developed, including: contrast-enhanced mammography, tomosynthesis, automated whole breast ultrasound, advanced MRI and molecular imaging (99mTc-MIBI gamma camera; 18F-FDG). However, early detection and differential diagnosis of malignant vs benign breast lesions remains a major challenge in patients with dense breasts. We have been developing novel approaches to early detection and differential diagnosis of malignant vs benign breast lesions using PET imaging of galectin-3 (Gal-3), that is significantly overexpressed in breast carcinomas, as compared to pre-malignant lesions. We developed a novel radiotracer 3-[18F]fluorophenylthio-digalactoside (18F-FPTDG) with high binding affinity (Kd 14 nM) and specificity to Gal-3. In vitro radiotracer binding studies in a panel of MCF10-derived cell lines with different degrees of malignancy and Gal-3 expression, demonstrated a highly significant linear relationship between the level of Gal-3 expression and the magnitude of 18F-FPTDG binding to cell membranes (R2 = 0.99). Preliminary in vivo PET imaging studies with 18F-FPTDG in mice bearing MCF10DCIS tumor xenografts demonstrated a rapid bi-exponential clearance of 18F-FPTDG from the blood (fast and slow clearance half-times: 0.5 and 10.5 min, respectively). 18F-FPTDG cleared predominantly via the hepatobiliary route, as evidenced by high levels of radioactivity in the liver, increasing levels in duodenum and upper intestinal tract. The liver and kidney clearance followed mono-exponential kinetics with half-times of ∼120 min and 37 min, respectively. Renal clearance was more active in mice, as evidenced by higher amounts of radioactivity in the bladder. The magnitude of catabolism of [18F]FPDTG was negligible, as evidenced by very low levels of [18F]F2 accumulation in the bone at 60-75 min post injection. The level of accumulation of [18F]FPDTG-derived radioactivity in the lungs, muscles, and other organs and tissues was extremely low. Also, there was no measurable levels of [18F]FPDTG-derived radioactivity in the brain. In contrast, there were distinct regions in the breast carcinoma xenograft with higher levels of [18F]FPDTG, especially in the central regions (hypoxia). The half-time clearance of [18F]FPDTG from tumors was ∼8 min, which was about twice longer than clearance half-time from lungs and muscles - 4.5 and 4 min, respectively. Additional studies are being conducted in various breast tumor xenograft models, as well as in PyVmT transgenic mice, to assess the utility of PET/CT with [18F]FPDTG for differential diagnosis of benign vs malignant breast lesions and for biopsy guidance. Citation Format: Robin E. Bonomi, Vadim Popov, Thomas Mangner, Avraham Raz, Anthony F. Shields, Juri G. Gelovani. PET imaging of galectin-3 expression with [18F]FPDTG for detection of early breast carcinoma lesions in dense breast tissue. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4232.

5-Oxo[1,3]dithiolo[4,5-d][1,3,2]dithiazol-1-ium chloride was converted into [(4-sulfanylidene-4H-1λ4,3,2-dithiazol-5-yl)sulfanyl]-formic acid esters and amides upon treatment with alcohols and amines, respectively; the structure of propyl [(4-sulfanylidene-4H-1λ4,3,2-dithiazol-5-yl)sulfanyl]formate was confirmed by X-ray diffraction.

N-Acyl tryptophan isopeptides undergo acyl transfer in chemical ligations via 7-, 10-, 11- and 12-membered cyclic transition states to yield natural peptides, representing the first examples of successful isopeptide ligations from N-acyl tryptophan units.