Delving into the Latest Updates on Institute of Chemical Biology and Fundamental Medicine SB RAS with Synapse

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Neoplasms

Skin and Musculoskeletal Diseases

Oncolytic virus

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A glimpse into the focused therapeutic areas

Technology Platform

Most used technologies in drug development

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Most frequently developed targets

Disease Domain	Count

Neoplasms	1

Top 5 Drug Type	Count

Oncolytic virus	1

Top 5 Target	Count

CSF-2R(Granulocyte-macrophage colony-stimulating factor receptor)	1

Abasic, or apurinic/apyrimidinic sites (AP sites) are among the most abundant DNA lesions, appearing in DNA both through spontaneous base loss and as intermediates of base excision DNA repair. Natural aldehydic AP sites have been known for decades and their interaction with the cellular replication, transcription and repair machinery has been investigated in detail. Oxidized AP sites, produced by free radical attack on intact nucleotides, received much attention recently due to their ability to trap DNA repair enzymes and chromatin structural proteins such as histones. In the past few years, it became clear that the reactive nature of aldehydic and oxidized AP sites produces a variety of modifications, including AP site-protein and AP site-peptide cross-links, adducts with small molecules of metabolic or xenobiotic origin, and AP site-mediated interstrand DNA cross-links. The diverse chemical nature of these common-origin lesions is reflected in the wide range of their biological consequences. In this review, we summarize the data on the mechanisms of modified AP sites generation, their abundance, the ability to block DNA polymerases or cause nucleotide misincorporation, and the pathways of their repair.

20 Jan 2025·Chemical Research in Toxicology

Polyamine Adducts with AP Sites: Interaction with DNA Polymerases and AP Endonucleases

Article

Author: Zharkov, Dmitry O. ; Amanova, Margarita M. ; Yudkina, Anna V.

Biological polyamines, such as spermine, spermidine, and putrescine, are abundant intracellular compounds mostly bound to nucleic acids. Due to their nucleophilic nature, polyamines easily react with apurinic/apyrimidinic (AP) sites, DNA lesions that are constantly formed in DNA by spontaneous base loss and as intermediates of base excision repair. A covalent intermediate is formed, promoting DNA strand cleavage at the AP site, and is later hydrolyzed regenerating the polyamine. Here we have investigated formation of AP site adducts with spermine and spermidine using sodium borohydride trapping technique and shown that they could persist in DNA for long enough to possibly interfere with cell's replication and transcription machinery. We demonstrate that both adducts placed internally into DNA are strongly blocking for DNA polymerases (Klenow fragment, phage RB69 polymerase, human polymerases β and κ) and direct dAMP incorporation in the rare bypass events. The internal AP site adducts with polyamines can be repaired, albeit rather slowly, by Escherichia coli endonuclease IV and yeast Apn1 but not by human AP endonuclease APE1 or E. coli exonuclease III, whereas the 3'-terminal adducts are substrates for the phosphodiesterase activities of all these AP endonucleases.

01 Dec 2024·Biochemical and Biophysical Research Communications

Properties of phosphoramide benzoazole oligonucleotides (PABAOs). II. Structure and hybridization efficiency of N-benzoxazole derivatives

Article

Author: Lomzov, Alexander A. ; Baranovskaya, Elizaveta E. ; Golyshev, Victor M. ; Gulyaeva, Oksana A. ; Yushin, Ivan I.

New phosphate-modified nucleic acid derivatives are of great significance in basic research and biomedical applications. We have recently developed a new class of phosphoramide benzoazole oligonucleotides (PABAOs). In this work, th properties of N-benzoxazole oligodeoxyribonucleotides have been thoroughly examined. We have demonstrated the convenient automated solid-phase synthesis of oligomers with a different number of modifications (up to six) at various positions. Optical properties, thermal stability, structure, and dynamics of PABAO/DNA complexes have been investigated. The N-benzoxazole-modified phosphate group is uncharged at neutral pH and has a pKa value of 8.52. Structural analysis performed by the CD spectroscopy and MD simulation indicate B-form of PABAO/DNA duplexes. The thermal stability of PABAO/DNA complexes bearing N-benzoxazole is reduced by 2.5-6.2° per modification compared to native duplexes at standard and near physiological buffer conditions. The performed study underlines a great potential of phosphoramide benzoazole oligonucleotides for basic research, applied sciences, and biotechnology.

100 Deals associated with Institute of Chemical Biology and Fundamental Medicine SB RAS

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100 Translational Medicine associated with Institute of Chemical Biology and Fundamental Medicine SB RAS

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Pipeline

Pipeline Snapshot as of 29 May 2025

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

VV-GMCSF-Lact(Oncostar) ( CSF-2R )	Breast Cancer More	Preclinical
VV-GMCSF-Apo(Institute of Chemical Biology and Fundamental Medicine) ( GM-CSF x RYBP )	Neoplasms More	Pending