Group of Bioconjugation
Group is engaged in developing methods of synthesis and studying of the conjugates properties of natural and biologically active substances, biopolymers (nucleic acids), organic fluorescent dyes, polycyclic aromatic compounds, stabilized carbocations, inorganic fluorescent nanocrystals and clusters.
Researchers are developing a substance with a high antiviral activity based on polycyclic aromatic hydrocarbon perylene. Group obtained a large number of compounds both nucleoside-based and non-nucleoside nature. These compounds have a broad spectrum of action, for example they can inhibit the replication of many enveloped viruses, such as herpes simplex virus, influenza, encephalitis, Hepatitis C etc.
The Group is engaged in the creation of fluorescent dyes to DNA probes. Researchers got functional derivatives of already both known and new dyes, as well as effective methods of its introduction in DNA probes, such fluorogenic DNA probes Taqman type or Molecular beacons for Real-Time PCR. The subject of the study is not only conjugates with dyes, but with proteins, as well as oligonucleotide-oligonucleotide conjugates which may serve as building blocks for assembling DNA nanostructures.
On the basis of stabilized carbocations are developed mass-spectrometric labels for biomolecules in a leaving (mass tags) and not cleaved off (derivatization) versions. In the first case are detected the actual labels which undergo analytical manipulation stage, being attached to the biomolecule, and then cleaved and detected on a mass spectrometer. In the second case, the ionic labels serve to improve the ionized analyzed molecules; the mass spectrum is detected a molecule conjugate with the label. Mass labels used for the detection of DNA mutations, for the determination of aminoglycoside and glycopeptide antibiotics, low molecular weight amines and thiols. For example, modification of low molecular weight volatile amines can easily detect them via HPLC, and reduce the detection limit of these amines.
The group collaborates with The Laboratory of Organic Synthesis, The Chumakov Institute of Poliomyelitis and Viral Encephalitis of the Russian Academy of Sciences, The Institute of Microbiology (Armenia), The Gause Research Institute of New Antibiotics, The Laboratory of Molecular Biology in Cambridge (UK), The Oxford University (UK), The Institute of Physical Organic Chemistry of the National Academy of Sciences (Belarus), The Center for nucleic acids (Denmark), The University of Alberta (Canada), The Cornell University (USA), The Indian Institute of Delhi Technologies (India) etc.
The Group of Bioconjugation was formed in 2010 as a result of the grant program "Molecular and Cellular Biology" of the Presidium of Russian Academy of Sciences for the new groups.
- Obtaining the compounds with antiviral activity.
- Creating the fluorescent DNA probes.
- Developing oligonucleotide conjugates as blocks for DNA nanostructures.
- Creating the mass-spectrometric labels for the detection of biomolecules.
- The formation of interchain excimer pyrene in the major groove of DNA (ChemBioChem, 2003, 4:841).
- 1-Phenylethynylpyrene was proposed as improved excimer forming fluorescent label for nucleic acids (Nucleosides Nucleotides, 1997, 16:1461; Eur. J. Org. Chem., 2004, 1298; Bioconjugate Chem., 2007, 18:1972) and used in various types of DNA probes (Mutation Res., 2006, 599:144; Meth. Mol. Biol., 2009, 578:209; Chem. Eur. J., 2008, 14:11010; Chem. Commun., 2010, 46:8362; Bioconjugate Chem., 2011, 22:533; Analyst, 2016, 141:1331).
- For the first time, fluorescent dyes were attached to a nucleobase through ethynyl linker (Биоорган. химия, 1996, 22:923; ChemBioChem, 2006, 7:810). A new class of antiviral compounds was found among these nucleosides. The compounds are active against herpes simplex virus type 1, hepatitis C virus and several other enveloped viruses (Биоорган. химия, 2003, 29:289; Вопросы вирусологии, 2006:34; Tetrahedron, 2006, 62:1279; Org. Biomol. Chem., 2006, 4:1091; PNAS USA, 2010, 107:17339; J. Virol., 2013, 87:3640; Med. Chem. Commun., 2016, 7:495).
- New mass-spectrometric labels were developed (Org. Biomol. Chem., 2008, 6:4593; Масс-спектрометрия, 2015, 12:253; Analyst, 2016, 141:3289) and the method of single nucleotide polymorphism detection using MALDI spectrometry was proposed (Anal. Chem., 2008, 80:2342; Meth. Mol. Biol., 2009, 578:345) and the analysis method of aminoglycoside antibiotics (Acta Naturae, 2016, 8:128).
- The application of azide-alkyne cycloaddition was revealed for the synthesis of DNA conjugates (Биоорган. химия, 2010, 36:437) including building blocks for the DNA nanostructures self-assembly (Изв. АН, Сер. хим., 2006:1220; Tetrahedron, 2008, 64:1467; Chem. Commun., 2013, 49:511; Org. Lett., 2014, 16:4590; Tetrahedron, 2016, 72:2386) and for the preparation of efficient fluorogenic DNA probes for real-time PCR assay (Anal. Bioanal. Chem., 2012, 404:59; Analyst, 2014, 139:2867; Analyst, 2016, 141:1331; Anal. Meth., 2016, 8:5826; Mol. Cell. Probes, 2016, 30:285).
|Vladimir Korshun, D.Sc||depart. email@example.com|
|Irina Stepanova||r. firstname.lastname@example.org|
|Anna Ponomarenko||PhD email@example.com|
New class of antiviral compounds: perylenyltriazoles (2017-11-20)
A new class of antiviral compounds has been found
Отчётная кампания по достижениям подразделений в 2015 г.
Обобщены данные о самособирающихся ДНК-наноструктурах и структурированных флуоресцентных ДНК- зондах (Ponomarenko A.I., Brylev V.A., Nozhevnikova E.V., Korshun V.A. Recent advances in self-assembled fluorescent DNA structures and probes. Curr. Top. Med. Chem., 2015, 15 (13), 1162–1178).
Предложена масс-спектрометрическая метка для аминов (Топольян А.П., Стрижевская Д.А., Слюндина М.С., Беляева М.А., Иванова О.М., Коршун В.А., Устинов А.В., Михура И.В., Формановский А.А., Борисов Р.С. Дериватизация первичных аминов катионом трис(2,6-диметоксифенил)метилия для анализа методом масс-спектрометрии МАЛДИ. Масс-спектрометрия, 2015, 12 (4), 253–258).