Sergey Burov

• Dr. Sci.
• Head of Department at Cytomed J.S.Co.

Peptide hydrazides are widely applied as precursors of peptide thioesters, valuable building blocks for the synthesis of proteins by native chemical ligation. In addition, they can be applied for the selective modification of cargo or carrier molecules using hydrazone ligation technique. In this work, we describe key aspects of solid phase synthesi...

Citation: Gileva, A.; Trushina, D.; Yagolovich, A.; Gasparian, M.; Kurbanova, L.; Smirnov, I.; Burov, S.; Markvicheva, E. Doxorubicin-Loaded Polyelectrolyte Multilayer Capsules Abstract: Recently, biodegradable polyelectrolyte multilayer capsules (PMC) have been proposed for anticancer drug delivery. In many cases, microencapsulation allows to conc...

Presently, most of anticancer drugs are high toxic for normal cells and, and as a result, they have severe side effects. Moreover, most of the formulations are lipophilic and have poor selectivity. To overcome these limitations, various drug delivery systems could be proposed. The aim of the current study was to fabricate novel polysaccharide nanoc...

Glioblastoma (GBM) is an aggressive and lethal form of brain cancer with a high invasion capacity and a lack of effective chemotherapeutics. Retinoid bexarotene (BXR) inhibits the neurospheroidal colony formation and migration of primary glioblastoma cells but has side effects. To enhance the BXR glioblastoma selectivity and cytotoxicity, we chemic...

Introduction Targeted multimodal approaches need to be strategically developed to control tumour growth and prevent metastatic burden successfully. Breast cancer presents a unique clinical problem because of the variety of cellular subtypes that arise. The tumour stage and cellular subtypes often dictate the appropriate clinical treatment regimen....

Introduction Core fucosylation of N-glycans on the integrin β1 subunit is essential for the functional activity of the integrin. The binding of α5β1 integrin with the tripeptide Arg-Gly-Asp (RGD) motif within the extracellular matrix protein fibronectin may be influenced by the α-1,6-fucose core or α-1,2-fucose and α-1,3/4-fucose peripheral N-glyca...

Introduction. Cutaneous melanoma is a challenge to treat due to rapid progression of disease and acquired resistance to therapy. Autophagy and the epithelial-to-mesenchymal transition (EMT) are closely interrelated and play a key role in tumor progression. Targeted co-inhibition of MEK and mTOR kinases is a potential target for melanoma therapy by...

Melanoma is one of the most aggressive and treatment-resistant tumors that responsible for majority of skin-cancer related deaths. Here we propose a combination of MEK inhibitor binimetinib with metformin as a promising therapy against human melanoma cells in vitro, including BRAF -mutated A375, Mel Z, and Mel IL cells, and NRAS-mutated Mel MTP and...

Engineering of a "smart" drug delivery system to specifically target tumour cells has been at the forefront of cancer research, having been engineered for safer, more efficient and effective use of chemotherapy for the treatment of cancer. However, selective targeting and choosing the right cancer surface biomarker are critical for a targeted treat...

Purpose: Multidrug resistance (MDR) of tumors to chemotherapeutics often leads to failure of cancer treatment. The aim of the study was to prepare novel MDR-overcoming chemotherapeutics based on doxorubicin (DOX) derivatives and to evaluate their efficacy in 2D and 3D in vitro models. Methods: To overcome MDR, we synthesized five DOX derivatives, a...

Background Prostaspheres-based three dimensional (3D) culture models have provided insight into prostate cancer (PCa) biology, highlighting the importance of cell–cell interactions and the extracellular matrix (EMC) in the tumor microenvironment. Although these 3D classical spheroid platforms provide a significant advance over 2D models mimicking i...

A practical protocol has been designed to synthesize dendronized polymeric chelating agents containing 1,4,7,10-tetraazacyclodocecane-N,N’,N’’,N‴-tetraacetic acid (DOTA) ligand. The efficiency of suggested approach was verified by grafting of N-vinylpyrrolidone-acrolein P(VP-Ac) copolymer with dendrons containing several DOTA residues as compared t...

Objectives: To design novel 3D in vitro co-culture models based on the RGD-peptide-induced cell self-assembly technique. Results: Multicellular spheroids from M-3 murine melanoma cells and L-929 murine fibroblasts were obtained directly from monolayer culture by addition of culture medium containing cyclic RGD-peptide. To reach reproducible arch...

Oxime ligation is a powerful tool in various bioconjugation strategies. Nevertheless, high reaction rates and quantitative yields are typically reported for aldehyde-derived compounds. In contrary, keto groups react much slower, with quantitative yields achieved at 5 h for low-molecular weight compounds and more than 15 h for polymers or dendrimers...

Multicellular tumor spheroids (MTS) have been at the forefront of cancer research, designed to mimic tumor-like developmental patterns in vitro. Tumor growth in vivo is highly influenced by aberrant cell surface-specific sialoglycan structures on glycoproteins. Aberrant sialoglycan patterns that facilitate MTS formation are not well defined. Matrix...

Development of novel anticancer formulations is a priority challenge in biomedicine. However, in vitro models based on monolayer cultures (2D) which are currently used for cytotoxicity tests leave much to be desired. More and more attention is focusing on 3D in vitro systems which can better mimic solid tumors. The aim of the study was to develop a...

In order to prepare polymeric contrast agents, various ways of modification of N-vinylpyrrolidone copolymers with vinylamine or acrolein with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid derivatives were investigated.

High toxicity, poor selectivity, severe side effects are major drawbacks of anticancer drugs. Various drug delivery systems could be proposed to overcome these limitations. The aim of the study was to fabricate polysaccharide microcontainers (MC) loaded with thymoquinone (TQ) by one-step ultrasonication technique and to study their cellular uptake...

Peptide hydrazides can be easily synthesized using a new hydrazone resin, obtained via acylation of aminomethyl polystyrene by Fmoc-hydrazone of pyruvic acid. It was shown that the hydrazone linker is completely stable in the course of standard Fmoc SPPS. Moreover, it can tolerate a treatment with 5% TFA/DCM thus permitting selective removal of Mtt...

The invention relates to the field of pharmaceutical chemistry, specifically to processes for preparing biologically active substances (BAS), in particular creatine amides. What is proposed is a process for preparing creatine amides which comprises treating creatine with para-toluenesulfonic acid in an organic solvent with subsequent reaction of th...

daily. Patients under 75 years received a dose of 220 mg dabigatran etexilate once daily. There was made preoperative haemostatic monitoring and also at the 7th, 14th, 21st, 28th and 35th postoperative day. The samples were taken 3 hours after application of dabigatran etexilate. The haemostatic tests were made by coagulometer BCS XP System versus1...

Novel water-soluble noncovalent adducts of the heterometallic copper subgroup complexes and human serum albumin (HSA) display strong phosphorescence, internalize into HeLa cells and can be used in time-resolved fluorescent imaging.

The neuroprotective activity of creatine amides – amino acid derivatives of creatine – was studied in a model of cerebral ischemia created by transient occlusion of the middle cerebral artery (OMCA) in rats. The neuroprotective effect of treatment with glycine (creatinylglycine ethyl ester acetate), phenylalanine (creatinyl-L-phenylalaninamide acet...

The invention relates to pharmaceutical chemistry notably to new biologically active substances (BAS) and their properties. In particular, the invention relates to Creatine derivatives having a general formula: NH═C(NH2)—N(CH3)—CH2—CO—NH—R*X, wherein R—amino acid residue of aliphatic, aromatic or heteroaromatic L-amino acid or its derivative repres...

A set of GnRH analogues containing nuclear localization signal (NLS) of SV-40 virus large T-antigen have been synthesized using solid phase peptide synthesis and chemical ligation technique. Selective chemical ligation was achieved as a result of hydrazone formation in the course of interaction between NLS hydrazide and GnRH analog modified by pyru...

A set of GnRH analogues containing the nuclear localization signal (NLS) of the SV-40 virus was synthesized using solid phase peptide synthesis and chemical ligation techniques. Selective chemical ligation was achieved through hydrazone formation upon the interaction of NLS hydrazide and GnRH analogue modified with pyruvic acid. The efficiency of t...

Prolonged oral creatine administration resulted in remarkable neuroprotection in experimental models of brain stroke. However, because of its polar nature creatine has poor ability to penetrate the blood-brain barrier (BBB) without specific creatine transporter (CRT). Thus, synthesis of hydrophobic derivatives capable of crossing the BBB by alterna...

We evaluated the efficacy of derivatives of creatine and amino acids (CrAA) for decreasing cerebral injury in rats with transient middle cerebral artery occlusion (MCAO). Neuroprotective effects of amides of creatine and glycine (CrGlyOEt), phenylalanine (CrPheNH2), thyrosine (CrTyrNH2), and GABA (CrGABAOEt) were investigated. Brain injury was eval...

With the goal of improving the efficacy of anticancer drugs due to the directed delivery to intracellular targets, a set of luliberin analogues containing the nuclear localization signal (NLS) of the SV-40 virus large T-antigen has been synthesized. The NLS was attached to the parent molecule via the D-lysine ɛ-amino group introduced into position...

To improve the efficiency of anticancer drugs due to their delivery to intracellular targets a set of GnRH analogues containing nuclear localization signal (NLS) of SV-40 virus large T-antigen have been synthesized. NLS was attached to the parent molecule via ε-amino group of D-Lysine in position 1 or 6 of peptide sequence using orthogonal protecti...

The rate and character of superficial tissue regeneration after wounds, burns, and other traumas depend on cell proliferation within the damaged area. The acceleration of wound healing via the stimulation of cell proliferation and extracellular matrix synthesis is one of the most important tasks of modern medicine. There are gene therapy approaches...

Genetic modification of mammalian embryos is an important way to model various changes in human development; also, it is an instrument for studying the functions of certain genes in mammals. Using our own experience in developing modes of delivery of genetic constructions to mammals in a nonviral way, we present here data on the delivery of a eukar...

The rate and character of skin tissue regeneration after wounds, burns and other traumas depend on the cell proliferation within damaged area. Acceleration of healing by stimulation of cell proliferation and extracellular matrix synthesis is one of the most important tasks of modern medicine. There are gene therapy approaches to wound treatment con...

N-terminal modification of peptides by unnatural amino acids significantly affects their enzymatic stability, conformational properties and biological activity. Application of N-amidino-amino acids, positively charged under physiological conditions, can change peptide conformation and its affinity to the corresponding receptor. In this article, we...

Phosphocreatine-Mg-complex acetate (PCr-Mg-CPLX) is a creatine-derived compound that in previous in vitro research was able to increase neuronal creatine independently of the creatine transporter, thus providing hope to cure the hereditary syndrome of creatine transporter deficiency. In previous research we showed that it reproduces in vitro the kn...

Some derivatives more lipophylic than creatine, thus theoretically being capable to better cross the blood-brain barrier, were studied for their protective effect in mouse hippocampal slices. We found that N-amidino-piperidine is harmful to brain tissue, and that phosphocreatine is ineffective. Creatine, creatine-Mg-complex (acetate) and phosphocre...

N-Protecting groups most widely used in peptides synthesis are examined. The possible mechanisms of the elimination of the protecting groups in acid and alkaline media are described and the methods of synthesis of the reactants for the introduction of certain protecting groups are considered. The bibliography includes 65 references.

The chemisorption of synthetic antigenic determinants of the human immunodeficiency virus on the surface of polystyrene microspheres with surface layers containing polystyrene-poly(vinylpyrrolidone) graft copolymers and carboxyl groups has been studied. The electrosurface properties of carrier particles before and after modification with peptides a...

This work was devoted to the study of conditions of the formation of DNA/K8 complex and analysis of factors effecting the entry of DNA/K8 complex into mammalian cells in comparison with DNA complexes with arginine-rich fragment (47-57) of human immunodeficiency virus (type 1) transcription factor Tat (Tat peptide). The stoichiometry of positively c...

N-Amidinoproline, a hybrid structure modeling key features of the Arg-Pro sequence, was synthesized. The activation of carboxyl group of free N-amidinoproline was found to result in the formation of a cyclic side product, whose structure was confirmed by ESI MS, 1H NMR, and 13C NMR spectra. The preparation of N-(mesitylenesulfonylamidino)-L-proline...

Hereditary creatine transporter deficiency causes brain damage, despite the brain having the enzymes to synthesize creatine. Such damage occurring despite an endogenous synthesis is not easily explained. This condition is incurable, because creatine may not be delivered to the brain without its transporter. Creatine-derived compounds that crossed t...

Luliberin analogues modified at the N-terminus were synthesized to search for drugs exerting a cytotoxic effect on cells of hormone-dependent tumors. A synthetic scheme effective in the preparation of analogues containing fatty acid residues was proposed. The cytotoxic effect of the peptides was studied on a number of cell lines of human tumors in...

Conformational computations of the synthesized H-Leu-His-Lys-Leu-Gln-Thr-NH2 and H-Ala-D-Ala-Lys-Leu-Ala-Thr-NH2 peptide sequences corresponding to the 16–21 fragment of salmon calcitonin II and its highly active analog that exhibits an analgesic activity were performed. The molecular dynamics method with the AMBER force field was used to trace cha...

Arginine-rich peptides, penetratins, as part of a number of cellular and viral proteins, can penetrate across plasma membrane directly, without participation of endocytosis. We show that one of penetratins, the basic domain 47-57 of human immunodeficiency virus, type 1, transcription factor Tat (Tat peptide), is able to interact with plasmid DNA el...

The delivery of "suicide" herpes simplex virus type-1 thymidine kinase gene (tk) into tumor cells, followed by treatment with synthetic nucleotide analogues (gancyclovir, acyclovir), is a perspective approach to cancer therapy. Serious limitations in employment of the existing means of gene delivery into target cells constitute the main obstacle fo...

The delivery of «suicide» herpes simplex virus type-1 thymidine kinase gene (tk) into tumor cells, followed by treatment with synthetic nucleotide analogues (gancyclovir, acyclovir), is a perspective approach to cancer therapy. Serious limitations in employment of the existing means of gene delivery into target cells constitute the main obstacle fo...

Effects of some fragments of alpha-calcitonine gene-related peptide (alpha-CGRP) on the collector lymphatic vessels of the rat small intestine mesenterium, were studied. All the fragments excepting alpha-CGRP (21-24) and (21-31) activate motility of the lymphatic vessels enhancing phasic contractions of the walls. Presence of aminoacid residuals in...

Dynorphin A (Dyn A) is a 17-residue opioid peptide derived from prodynorphin precursors found in mammalian tissues. Removal of Tyr1 from Dyn A produces a peptide that is more potent than Dyn A in attenuating the acute phase of the inflammatory response, as measured by inhibition of heat-induced edema in the anesthetized rat's paw (exposure to 58 de...

We have analyzed the serum from patients with refractory epilepsy for the presence of autoreactive antibodies to AMPA glutamate receptor subunits. The presence and the level of autoantibodies were assessed using immunoblot and ELISA with synthetic peptides specific for subregions of AMPA glutamate receptor subunits. Patients with refractory epileps...

We have developed a novel synthetic peptide containing both the antiadhesive Arg-Gly-Asp (RGD) amino acid sequence and a nitric oxide (NO) moiety well known for its vasorelaxant properties. The main objective of this study was to determine whether this hybrid molecule is concurrently effective with regard to antithrombotic and vasorelaxation action...

The ability of the antitumor analogs of luliberin (LH-RH), a hypothalamic peptide hormone, to stimulate the immune function of T cells is examined in experiments with the gene coding for interleukin-2 (IL-2). Recombinant MIL2C or 4×Pu DNA containing the marker gene of chloramphenicol acetyltransferase (CAT) under the control of a 2.2 kb promoter of...

Fragments of the calcitonin gene-related neuropeptide's molecule with the amino acid sequence 1-9, 10-20, 15-24, 20-29 and 30-37, were studied. The fragment 20-29 revealed the greatest biological activity: it induced a dose-dependent drop of arterial pressure in i.v. administration, enlarges arterial and venous microvessels when locally applied.

The synthesis of analogs of the hormone has been described in the literature [2, 3], and the biological activities of individual fragments of .the natural molecule have been investigated. The majority of such investigations have been devoted to the structure-activity relationship in the N-terminal part of the CGRP molecule [4, 5]. Together with thi...

With the aim of obtaining antitumoral drugs possessing a binary action mechanism, we have synthesized a series of shortened analogs of luliberin, including some containing a 1-carboxymethyl-5-fluorouracil residue. Their antitumoral and hormonal activities have been investigated.

The release of oxytocin, arginine-8-vasopressin and oestradiol-17β by bovine granulosa cells in culture was analysed either with or without LH-releasing hormone (LHRH), its agonists (cyclo [Pro ¹ d Phe ⁶ ] LHRH and des 1–3, 10[ d Ala ⁶ ] LHRH) or antagonists ([ d Phe ² d Phe ⁶ ] LHRH, [ d Phe ² d Phe(NH 2 ) ⁶ ] LHRH or cyclo [Pro ¹ d Phe ² d Phe ⁶...

A number of fragments of salmon calcitonin II possessing analgesic activity of the nonopioid type have been synthesized.

The influence of some immunomodulation peptides SKD, R and L on the interleukin-2 (IL-2) synthesis in T-lymphocytes and possibility of their specific interaction with nucleotide sequences of IL-2 gene were studied. It was firstly shown that peptides R and L specifically interacted with regulatory nucleotide sequences of IL-2 gene and, possibly, pla...

UDC 577.21:576.3)

A new cyclic analogue of luliberin possessing the capacity for stimulating ovulation in sexually mature and infantile rats and also exhibiting a pronounced prolongation of its influence on a number of behavioral reactions of animals has been synthesized.

Five new luliberin analogues with shortened amino acid sequences have been synthesized. The different variants for obtaining the compounds under consideration are discussed. In an investigation of the biological activities of the analogues it was shown that they possess a pronounced action of the course of the ovulation processes in experimental an...

1. A linear analog of luliberin is a luliberin antagonist, whereas a cyclic analog is a superagonist of it. 2. Pharmacological tests of the cyclic luliberin analog and its linear precursor confirmed the hypothesis of a quasicyclic structure of the biologically active conformation of luliberin.

A study was made of the cyclic LH-RH analog and its linear precursor on infantile and mature female rats. The compounds showed various biological properties which manifested themselves in their effects on ovulation. The linear analog proved to be an antagonist and the cyclic analog the LH-RH agonist. A hypothesis to the effect that the LH-RH biolog...

The effects of synthetic neuropeptide LH-RH and its analogues were studied in experiments on 174 white male rats. The influence of the substances was shown on instrumental avoidance learning in Y-shaped maze. Convulsive and anticonvulsive effects of the preparations were studied on experimental model of corasol seizures. The analgetic effect of the...

Two new analogs of the releasing factor of the luteinizing hormone with shortened amino acid sequences have been synthesized by the methods of classical peptide chemistry. The influence of the preparations on the action of chorionic gonadotropin and on the course of processes of ovulation in experimental animals has been studied. The promising natu...

In order to study the influence of substituents of the aromatic ring of D-phenyl-alanine on the inhibiting capacity of luliberian analogs, we have synthesized two new analogs: and luliberin. The synthesis was performed by the fragmentary condensation method using 2+(3+5) and 2+(5+3) schemes. A new and convenient method of obtaining the amide of...