D-amino acids

D-aminokiseline su stereoizomeri L-aminokiselina. Često se nazivaju neprirodnim aminokiselinama, zbog toga što se dugo vremena smatralo da se D-aminokiseline nalaze samo u nižim organizmima te se njihova prisutnost u tkivima eukariota smatrala neprirodnom. Međutim nekoliko D-aminokiselina nađeno je u mozgu sisavaca. Prednji dio mozga obiluje D-serinom, koji je kofaktor N-metil-D-aspartatnih receptora (NMDA) i potiče neurotransmisiju. D-aminokiselinska oksidaza (DAO), čija je uloga kataliza oksidacijske deaminacije neutralnih i bazičnih aminokiselina, u najvećem dijelu se nalazi u prednjem dijelu mozga. DAO katabolizira D-serin i zbog toga regulira neurotransmisiju. U mozgu mutiranih miševa koji nemaju DAO gen, došlo je do povećanja koncentracije D-serina i ostalih D-aminokiselina. Povećanje koncentracije D-serina utječe na funkcioniranje NMDA receptora, pa dolazi do promjena u mozgu mutiranih miševa. DAO i D-serin imaju važnu ulogu u razvoju mozga i sinaptičkoj plastičnosti. DAO je također povezan i s odgovorom na bol i šizofrenijom. D-aminokiseline su nužne komponente peptidoglikana (PG) bakterija i problemi u njihovoj sintezi dovode do smrti stanice. Peptidoglikan se sastoji od šećera i oligopeptida. Transpeptidaze povezuju oligopeptidne lance peptidogilkana i tako omogućuju stjenci čvrstoću i oblik. Transpeptidaze su zadužene i za ugradnju D-aminokiselina u peptidoglikan. D-aminokiseline se sintetiziraju racemizacijom ili epimerizacijom -ugljikova atoma pripadajuće L-aminokiseline pomoću D-aminokiselinskih racemaza ili D-aminokiselinskih epimeraza. Reakcija sinteze (racemizacija) D-aminokiselina zasniva se na otpuštanju protona sa -ugljikova atoma pri čemu nastaje karbanionski međuprodukt, koji se zatim protonira. Smjer iz kojeg se proton dodaje karbanionskom međuproduktu određuje kiralnost nastale aminokiseline. Aminokiselinske racemaze i epimeraze se dijele na dva razreda, ovisno o tome sadrže li prostetičku skupinu (piridoksal-5-fosfat, PLP) ili ne. Aminokiseline se mogu sintetizirati i stereospecifičnom aminacijom odgovarajuće -ketokiseline pomoću enzima transaminaza. Transaminaze poput racemaza i epimeraza kataliziraju reverzibilne reakcije i imaju prostetičku skupinu PLP, ali se razlikuju u mehanizmu reakcije

Application of triarylborane system in selective readout of nucleic acids and live cell fluorescence imaging

Detekcijske metode se baziraju na fluorescencijskim biljezima koji se koriste za obilježavanje proteina, određenih DNA/RNA sekvenci i sl. Oni se na DNA/RNA sekvence mogu vezati u utor, interkalirati ili ostvarivati elektrostatske interakcije. U ovom istraživanju spektroskopski i kalorimetrijski su okarakterizirane interakcije dva triarilboranska derivata SG224 i SG216 s nizom jednolančanih i dvolančanih polinukleotida. Spoj SG216 se ne veže na polinukleotide. Spoj SG224 se veže na DNA/RNA strukture kombinacijom više različitih načina te nije selektivn prema jednolančanim ili dvolančanim polinukleotidima ni prema DNA ili RNA uzvojnicama. Istovremeno s procesom vezanja odvija se i neki drugi proces, vjerojatno agregacija spoja, te se zbog toga ne može preciznije odrediti način vezanja. Pretpostavlja se da je vezanje u utor najznačajniji način vezanja, što potvrđuje i činjenica da SG224 ne pokazuje afinitet k vezanju p(dGdC)2 niza, čiji je utor sterički blokiran. Spoj se može koristiti kao spektropolarimetrijski biljeg za pdA sekvence, jer se prilikom vezanja spoja na pdA sekvence inducira jaki CD signal na 402 nm. Spoj nema značajan antiproliferativan učinak.Detection methods are based on fluorescence markers which are used for marking proteins, certain DNA/RNA sequences etc. They bind into the groove, intercalate or achive electrostatic interactions with DNA/RNA sequences. In this research we spectroscopically and calorimaterically characterize interactions between two three-aryl-borane derivatives SG224 and SG216 with series of single - and double-stranded polynucleotides. Compound SG216 does not bind to the polynucleotides. Compound SG224 binds to DNA/RNA structures in several different patterns. However, it´s not selective for neither single- nor double-stranded polynucleotides or to DNA/RNA helixes. Simultaneously with the binding process, another process also occurs – most likely aggregation of the compound. Therefore the binding method cannot be precisely defined. It´s however assumed that binding into the groove is most likely as it was confirmed by the fact SG224 does not show affinity to bind p(dGdC)2 string, whose groove is sterically blocked. Compound can be used as spectro-polarimetric marker for pdA sequences, due to big CD signal on 402 nm that is induced when SG224 binds pdA sequences. The compound does not have significant antiproliferative effect

Application of triarylborane system in selective readout of nucleic acids and live cell fluorescence imaging

Detekcijske metode se baziraju na fluorescencijskim biljezima koji se koriste za obilježavanje proteina, određenih DNA/RNA sekvenci i sl. Oni se na DNA/RNA sekvence mogu vezati u utor, interkalirati ili ostvarivati elektrostatske interakcije. U ovom istraživanju spektroskopski i kalorimetrijski su okarakterizirane interakcije dva triarilboranska derivata SG224 i SG216 s nizom jednolančanih i dvolančanih polinukleotida. Spoj SG216 se ne veže na polinukleotide. Spoj SG224 se veže na DNA/RNA strukture kombinacijom više različitih načina te nije selektivn prema jednolančanim ili dvolančanim polinukleotidima ni prema DNA ili RNA uzvojnicama. Istovremeno s procesom vezanja odvija se i neki drugi proces, vjerojatno agregacija spoja, te se zbog toga ne može preciznije odrediti način vezanja. Pretpostavlja se da je vezanje u utor najznačajniji način vezanja, što potvrđuje i činjenica da SG224 ne pokazuje afinitet k vezanju p(dGdC)2 niza, čiji je utor sterički blokiran. Spoj se može koristiti kao spektropolarimetrijski biljeg za pdA sekvence, jer se prilikom vezanja spoja na pdA sekvence inducira jaki CD signal na 402 nm. Spoj nema značajan antiproliferativan učinak.Detection methods are based on fluorescence markers which are used for marking proteins, certain DNA/RNA sequences etc. They bind into the groove, intercalate or achive electrostatic interactions with DNA/RNA sequences. In this research we spectroscopically and calorimaterically characterize interactions between two three-aryl-borane derivatives SG224 and SG216 with series of single - and double-stranded polynucleotides. Compound SG216 does not bind to the polynucleotides. Compound SG224 binds to DNA/RNA structures in several different patterns. However, it´s not selective for neither single- nor double-stranded polynucleotides or to DNA/RNA helixes. Simultaneously with the binding process, another process also occurs – most likely aggregation of the compound. Therefore the binding method cannot be precisely defined. It´s however assumed that binding into the groove is most likely as it was confirmed by the fact SG224 does not show affinity to bind p(dGdC)2 string, whose groove is sterically blocked. Compound can be used as spectro-polarimetric marker for pdA sequences, due to big CD signal on 402 nm that is induced when SG224 binds pdA sequences. The compound does not have significant antiproliferative effect

The Nature of the (Oligo/Hetero)Arene Linker Connecting Two Triarylborane Cations Controls Fluorimetric and Circular Dichroism Sensing of Various ds-DNAs and ds-RNAs

A series of tetracationic bis-triarylborane dyes, differing in the aromatic linker connecting two dicationic triarylborane moieties, showed very high submicromolar affinities toward ds-DNA and ds-RNA. The linker strongly influenced the emissive properties of triarylborane cations and controlled the fluorimetric response of dyes. The fluorene-analog shows the most selective fluorescence response between AT-DNA, GC-DNA, and AU-RNA, the pyrene-analog’s emission is non-selectively enhanced by all DNA/RNA, and the dithienyl-diketopyrrolopyrrole analog’s emission is strongly quenched upon DNA/RNA binding. The emission properties of the biphenyl-analog were not applicable, but the compound showed specific induced circular dichroism (ICD) signals only for AT-sequence containing ds-DNAs, whereas the pyrene-analog ICD signals were specific for AT-DNA with respect to GC-DNA, and also recognized AU-RNA by giving a different ICD pattern from that observed upon interaction with AT-DNA. The fluorene- and dithienyl-diketopyrrolopyrrole analogs were ICD-signal silent. Thus, fine-tuning of the aromatic linker properties connecting two triarylborane dications can be used for the dual sensing (fluorimetric and CD) of various ds-DNA/RNA secondary structures, depending on the steric properties of the DNA/RNA grooves

Application of triarylborane system in selective readout of nucleic acids and live cell fluorescence imaging

Detekcijske metode se baziraju na fluorescencijskim biljezima koji se koriste za obilježavanje proteina, određenih DNA/RNA sekvenci i sl. Oni se na DNA/RNA sekvence mogu vezati u utor, interkalirati ili ostvarivati elektrostatske interakcije. U ovom istraživanju spektroskopski i kalorimetrijski su okarakterizirane interakcije dva triarilboranska derivata SG224 i SG216 s nizom jednolančanih i dvolančanih polinukleotida. Spoj SG216 se ne veže na polinukleotide. Spoj SG224 se veže na DNA/RNA strukture kombinacijom više različitih načina te nije selektivn prema jednolančanim ili dvolančanim polinukleotidima ni prema DNA ili RNA uzvojnicama. Istovremeno s procesom vezanja odvija se i neki drugi proces, vjerojatno agregacija spoja, te se zbog toga ne može preciznije odrediti način vezanja. Pretpostavlja se da je vezanje u utor najznačajniji način vezanja, što potvrđuje i činjenica da SG224 ne pokazuje afinitet k vezanju p(dGdC)2 niza, čiji je utor sterički blokiran. Spoj se može koristiti kao spektropolarimetrijski biljeg za pdA sekvence, jer se prilikom vezanja spoja na pdA sekvence inducira jaki CD signal na 402 nm. Spoj nema značajan antiproliferativan učinak.Detection methods are based on fluorescence markers which are used for marking proteins, certain DNA/RNA sequences etc. They bind into the groove, intercalate or achive electrostatic interactions with DNA/RNA sequences. In this research we spectroscopically and calorimaterically characterize interactions between two three-aryl-borane derivatives SG224 and SG216 with series of single - and double-stranded polynucleotides. Compound SG216 does not bind to the polynucleotides. Compound SG224 binds to DNA/RNA structures in several different patterns. However, it´s not selective for neither single- nor double-stranded polynucleotides or to DNA/RNA helixes. Simultaneously with the binding process, another process also occurs – most likely aggregation of the compound. Therefore the binding method cannot be precisely defined. It´s however assumed that binding into the groove is most likely as it was confirmed by the fact SG224 does not show affinity to bind p(dGdC)2 string, whose groove is sterically blocked. Compound can be used as spectro-polarimetric marker for pdA sequences, due to big CD signal on 402 nm that is induced when SG224 binds pdA sequences. The compound does not have significant antiproliferative effect