A véralvadás XIII-as faktora szubsztrátjaként szolgáló, illetve a XIII-as faktort gátló peptidek és peptid analógok szintézise és hatásuknak a vizsgálata = The synthesis and testing of peptides and peptide analogue compounds which serve as substrates or inhibitors of blood coagulation Factor XIII

A kutatási program első felében aktivált XIII-as faktor (FXIIIa) szubsztrátokat kerestünk, majd olyan oligopeptideket próbáltunk előállítani, melyek a FXIIIa-t gátolják. A FXIII a véralvadási kaszkád utolsó szakaszában aktiválódik trombin és Ca2+ együttes hatására. Fő fiziológiás funkciója a fibrinláncok keresztkötése és az alfa2-plazmin inhibitornak (alfa2-PI), a fibrin polimerekhez való kötése. Egy olyan glutamin donor szubsztrátot készítettünk: Asn-Gln-Glu-Gln-Val-Ser-Pro-Leu-Thr-Leu-Leu-Lys (P12), mely megfelel az alfa2-PI N-terminális szekvenciájának. 1, A P12 fenti szekvenciájából kiindulva egyesével lecsökkentettük a szubsztrát tagszámát egészen négy aminosavig (Asn-Gln-Glu-Gln) és megszintetizáltuk az oligopeptideket. A tizenegytagú majdnem olyan jó szubsztrát, mint a dodekapeptid, míg a tíztagú erősebb kötődést, de valamivel kisebb aktivitást mutatott. A kilenctagúaktól rövidebbek lényegesen kisebb enzimaktivitást és kötődést adtak. 2, A szubsztrátként még jól használható oligopeptidek bizonyos aminosavait szisztematikusan más aminosavakkal cseréltük ki (Ser-Gly és Leu-Gly). A kapott eredmények alapján az a tíztagú peptid bizonyult a legmegfelelőbb szubsztrátnak, amelyiknek a 10-es pozíciójában a Leu helyett Gly van. 3, A gátlás vizsgálatánál azok a peptidek jöhettek számításba, amelyeknek kicsi a szubsztrát aktivitása, de elég jól gátolják FXIIIa-t. Sajnos nem találtunk számottevő gátlást mutató vegyületet. | In the first part of our research program we tried to find different substrates for activated Factor XIII (FXIIIa), later we synthesized oligopeptides which can inhibit FXIIIa. Factor XIII is activated in the last step of the coagulation cascade by the concerted action of thrombin and calcium ions. The main physiological function of FXIII is the cross-linking of fibrin chains and the linking of alfa2-plasmin inhibitor (alfa2PI) to the fibrin polymers. We synthesized a glutamine donor substrate Asn-Gln-Glu-Gln-Val-Ser-Pro-Leu-Thr-Leu-Leu-Lys (P12) corresponding to the N-terminal sequence of alfa2PI. 1, Starting with the sequence of P12 we tried to reduce the number of the amino acids from 12 to 4 (Asn-Gln-Glu-Gln) and synthesized the corresponding oligopeptide sequences. P11 oligopeptide substrate was quite as good as P12, while P10 showed stronger affinity to the enzyme, but less activity. Shorter peptides showed significantly less enzyme activity and poor binding. 2, In the next step, we systematically changed some of the amino acids in the original sequence (P12) with other amino acids (Ser-Gly and Leu-Gly). The best substrate proved to be the following: Asn-Gln-Glu-Gln-Val-Ser-Pro-Leu-Thr-Gly. 3, During the inhibition experiments we considered peptides with little substrate activity but still inhibiting Factor XIII. Unfortunately no considerable amount of compounds inhibiting FXIIIa could be found

Oligoester and Polyester Production via Acido-alcoholysis of PET Waste

A new chemical way has been introduced to recycle poly(ethylene terephthalate) via acido-alcoholysis. Acido-alcoholysis has been developed as a green way to produce oligoesters from PET waste which can be used as building blocks to new compostable polyesters. Organic acids and 1,4-butanediol were used as reagents. The solvolysis products were further reacted with diglycidyl ethers of different diols to obtain higher molecular weight polyesters. The resulted materials were tested with GPC, FTIR, TGA, functional group analysis methods and composting. It was found that the reagents in acido-alcoholysis fully incorporated into the reaction product obtaining oligoesters with carboxyl and hydroxyl end groups. Significant mass loss and fragmentation was observed on oligo- and polyesters after composting

Poli(etilén-tereftalát) bontása visszaforgatható organokatalizátorok segítségével: Depolymerization of poly(ethylene terephthalate) in the presence of recyclable organocatalysts

Recycling of plastic materials has an important role in the twenty-first century in reducing environmental pollution and saving petroleum resources. Poly(ethylene terephthalate) (PET) provides one of the best examples for this as it is a non-biodegradable polymer that is mainly used as raw material for a wide range of packaging applications, making degradation of PET a subject of great interest for researchers. In our work, post-consumer PET bottles were degraded with glycolysis into bis(2-hydroxyethyl) terephthalate (BHET) monomer using commercially available functionalized silica gels or 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) immobilized on silica gel. After the most stable and active catalyst was found to be triethyl amine functionalized silica gel, the optimization of reaction parameters was carried out. The silica gel as solid support helps in recycling the applied organic base making this process sustainable. Kivonat A műanyagok újrahasznosítása rendkívüli fontosságú a huszonegyedik században, mind a környezetszennyezés csökkentése, mind pedig a meg nem újuló energiaforrások megtakarítása miatt. A poli(etilén-tereftalát) (PET) az egyik legjobb példa erre, mivel ez egy biológiailag nem lebomló polimer, melyet főleg csomagoláshoz használnak fel széles körben, ezért ennek a műanyagnak a lebontása nagy érdeklődést váltott ki a kutatókból. Munkánk során használt PET-palackokat bontottunk le glikolízissel bisz(2-hidroxietil)-tereftalát (BHET) monomerré kereskedelmi forgalomban kapható funkcionalizált szilikagél, vagy szilikagélhez rögzített 1,5,7-triazabiciklo[4.4.0]dec-5-ént (TBD) katalizátorokat alkalmazva. Miután azt találtuk, hogy a legstabilabb és legaktívabb katalizátor a trietil-amin funkcionalizált szilikagél, optimalizáltuk a reakcióparamétereket. A szilikagél szilárd hordozóként lehetővé teszi az alkalmazott szerves bázis visszaforgatását, így fenntarthatóvá téve a folyamatot

A gazdaságok jövedelmének és a mezőgazdaság üzemszerkezetének várható változása 2010-ig

Kiadványunk arra kereste a választ, hogy az SPS rendszer bevezetésével párhuzamosan milyen változások várhatók a mezőgazdasági termelés jövedelmezőségében és a termelés szerkezetében

Synthesis and applications of cinchona squaramide‐modified poly (glycidyl methacrylate) microspheres as recyclable polymer‐grafted enantioselective organocatalysts

Our work presents the immobilization of cinchona squaramide organocatalyst on poly(glycidyl methacrylate) solid support. Preparation of the well-defined monodisperse polymer microspheres was facilitated by comprehensive parameter optimization. Exploiting the reactive epoxy groups of the polymer support, three amino-functionalized cinchona derivatives were immobilized on this carrier. To explore the effect of the amino-linker, these structurally varied precatalysts were synthesized by modifying the cinchona skeleton at different positions. The catalytic activities of the immobilized organocatalysts were tested in Michael addition reaction of pentane-2,4-dione and trans--nitrostyrene with excellent yields (up to 98%) and enantioselectivities (up to 96% ee).Finally, the catalysts were easily recovered five times by centrifugation without loss of activity

A véralvadás XIII-as faktora: strukturális és funkcionális vonatkozások, jelentősége különböző kórképekben = Blood coagulation FXIII: structural, functional aspects, its involvement in various pathological conditions

Új megállapításokat tettünk a FXIII plazmában történő aktivációjára, a két alegység (FXIII-A és FXIII-B) egymáshoz kapcsolódásának strukturális elemeire és a FXIIIa-glutamin szubsztrát kapcsolatra vonatkozóan. Új módszereket dolgoztunk ki a FXIII aktivitás mérésére, a FXIII-A intracelluláris detektálására. Utóbbi bevezetésre került a leukémiák diagnosztikájában. Immunoassay-t dolgoztunk ki az a2 plazmin inhibitor két izoformájának mennyiségi meghatározására. 10 FXIII-A hiányos betegen derítettük fel a háttérben álló mutációkat és ezek következményeit a fehérje strukturájára-funkciójára. Kísérletesen bizonyítottuk, hogy a plazma FXIII hiánya sebgyógyulási zavart okoz. Kimutattuk, hogy myocardiális infarctuson (MI) átesett nőkben emelkedett a plasma FXIII szintje és az emelkedett FXIII szint 2,5-3,0 szorosra fokozza az MI rizikóját, ami kizárólag nőkön érvényesül. 16 cikk metaanalízisiével a FXIII-A L34 allél szignifikáns védőhatását lehetett kimutatni a coronaria betegség ellen, a polimorfizmus a nagy rizikóju magyar populációban azonban csak emelkedett fibrinogén szint esetén védő hatású. A L/L homozigóták FXIII szintje MI-ben szignifikánsan alacsonyabb a vad típusúakénál. Csontvelő abláció után csökken, magas thrombocyta számmal járó myeloproliferatív betegségben emelkedik a FXIII szintje. Bronchoalveoláris mosófolyadékban kimutatható az alveoláris macrophagokból származó FXIII-A, chronicus bronchitisben ennek szintje emelkedik, s esetenként megjelenik a plazma FXIII is. | New results were reported on the activation of factor XIII (FXIII) in plasma, on the structural elements involved in the association of FXIII subunits (FXIII-A and FXIII-B) and on the interaction of activated FXIII (FXIIIa) with its glutamine substrate. Methods were developed for the determination of FXIII activity and the intracellular detection of FXIII-A by flow cytometry. The latter was introduced in the diagnostics of leukemias. Immunoassay was developed for the determination of the two isoforms of a2 plasmin inhibitor. The mutations causing FXIII-A deficiency were identified in 10 patients and their consequences were explored at the protein level. The involvement of FXIII in would healing was proven. It was shown that in women with the history of myocardial infarction (MI) FXIII level was elevated and elevated FXIII level represented a 2.5-3.0-fold increased risk of MI in women, but not in men. A protective effect of the FXIII-A L34 allele against MI was demonstrated by metaanalysis of 16 articles. In the Hungarian population this protective effect prevailed only at high fibrinogen level. FXIII level was decreased in L/L homozygotes with the history of MI. Bone marrow ablation decreased plasma FXIII level, while myeloproliferative diseases increased it. In the bronchoalveolar lavage fluid FXIII-A derived from alveolar macrophages was detected, in inflammatory bronchoalveolar diseases FXIII-A level increased and occasionally plasma FXIII was also be present

Effect of Composting on the Behavior of Polyolefin Films - A True-to-Life Experiment

Commercial polypropylene (PP), high-, medium- and low density polyethylene (HDPE, MDPE, LDPE) films, as well as MDPE films containing pro-oxidative additives and thermoplastic starch (TPS) were composted for six weeks together with biologically degradable films, such as poly (lactic acid) (PLA), Ecovio (BASF), Mater Bi(Novamont) and cellophane. Visual appearance of the polyolefin-based films did not change significantly, while the biologically degradable films fell apart. Thickness and mechanical properties of the polyolefin-based films also did not vary significantly after composting. The thickness of the degradable films however increased due to biofilm formation and finally decreased due to biodegradation, and their mechanical properties drastically dropped. FTIR proved the formation of carbonyl absorption of commercial and of the additive-containing films respectively) after composting due to oxidation. The FTIR-spectrum of the biodegradable films showed drastic change after composting. Formation of free radicals was detectable by ESR-spectroscopy, if pro-oxidative additive containing MDPE film was exposed for one week to sunlight, and the intensity of free radical formation increased after composting. The number-average molecular mass of MDPE films containing pro-oxidative additives decreased, low molecular mass fractions appeared and polydispersity increased after composting. Commercial polyolefin films were covered by microorganisms much more densly than films containing pro-oxidative additives detected by SEM. Even TPS did not increase the quantity of microorganisms. Biodegradable films were densly covered by microorganisms of different types and they became porous and holes were observable on their surface. It can be concluded that composting had no significant effect on the behaviour of the commercial PP and PE films. Signs of initial degradation were observable on MDPE films with pro-oxidative additives and TPS after 6 weeks composting, although it cannot be considered as biological degradation. Non of the tested polyolefin films suffered such degree of degradation in compost, as the biologically degradable films. It may be concluded that polyolefin films neither degrade in compost nor they undergo biodegradation

Encoding Information into Polyethylene Glycol Using an Alcohol-Isocyanate “Click” Reaction

In this article, the capability of encoding information using a homologous series of monodisperse monomethoxypolyethylene glycols (mPEG), with a number of ethylene oxide units ranging from nEO = 5 to 8, and monodisperse linear aliphatic isocyanates containing a number of CH2 units from 3 to 7, is demonstrated. The “click” reaction of the two corresponding homologous series yielded 20 different isocyanate end-capped polyethylene glycol derivatives (mPEG-OCONHR) whose sodiated adduct ion’s nominal m/z values spanned from 360 to 548, providing an average ca. 8 m/z unit for the storage of one-bit information. These mPEG-OCONHR oligomers were then used to encode information in binary sequences using a 384-well MALDI sample plate and employing the common dried-droplet sample preparation method capable of encoding 20 bit, i.e., 2.5 byte information in one spot, was employed. The information stored in the spots was read by MALDI-TOF MS using the m/z value of the corresponding mPEG-OCONHR oligomers. The capability of the method to store data was demonstrated by writing and reading a text file, visualizing a small picture and capturing a short audio file written in Musical Instrument Digital Interface (MIDI) sequence. Due to the very large similarities in the chemical structures of the encoding oligomers and their “easy to be ionized” property, as well as their very similar ionization efficiencies, the MALDI-TOF MS signal intensities from each compound was so strong and unambiguous that complete decoding could be performed in each case. In addition, the set of the proposed encoding oligomers can be further extended to attain higher bit “densities”