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Obnovit | RAW

Institute of Organic Chemistry and Biochemistry of the CAS, v. v. i.

List of available PhD theses

Approaches to the Total Synthesis of Fumiquinazoline-Based Pyrazinoquinazoline Alkaloids and Analogs

Department: Department of Organic Chemistry, Faculty of Chemical Technology
Study programmes: Chemie, Chemistry
Theses supervisor: Dr. habil. Ullrich Jahn

Annotation

In this project, short and bioinspired synthetic approaches to complex fumiquinazoline-based pyrazinoquinazoline alkaloids will be developed. The total syntheses will be modular and aimed at investigating their biological profiles in collaboration. Small focussed libraries of analogs are envisaged to complement the total syntheses of the natural products.

Approaches to the Total Synthesis of Fumiquinazoline-Based Pyrazinoquinazoline Alkaloids and Analogs

Department: Department of Chemistry of Natural Compounds, Faculty of Food and Biochemical Technology
Theses supervisor: Dr. habil. Ullrich Jahn

Annotation

In this project, short and bioinspired synthetic approaches to complex fumiquinazoline-based pyrazinoquinazoline alkaloids will be developed. The total syntheses will be modular and aimed at investigating their biological profiles in collaboration. Small focussed libraries of analogs are envisaged to complement the total syntheses of the natural products.

Approaches to the Total Synthesis of Glyantrypine-Based Pyrazinoquinazoline Alkaloids and Analogs

Department: Department of Organic Chemistry, Faculty of Chemical Technology
Study programmes: Chemie, Chemistry
Theses supervisor: Dr. habil. Ullrich Jahn

Annotation

In this project, short and bioinspired synthetic approaches to complex glyantrypine-based pyrazinoquinazoline alkaloids will be developed. The total syntheses will be modular and aimed at investigating their unknown biological profiles in collaboration. Small focussed libraries of analogs are envisaged to complement the total syntheses of the natural products.

Approaches to the Total Synthesis of Glyantrypine-Based Pyrazinoquinazoline Alkaloids and Analogs

Department: Department of Chemistry of Natural Compounds, Faculty of Food and Biochemical Technology
Theses supervisor: Dr. habil. Ullrich Jahn

Annotation

In this project, short and bioinspired synthetic approaches to complex glyantrypine-based pyrazinoquinazoline alkaloids will be developed. The total syntheses will be modular and aimed at investigating their unknown biological profiles in collaboration. Small focussed libraries of analogs are envisaged to complement the total syntheses of the natural products.

BODIPY-Based Systems for Release of Signalling Molecules and Modulation of Biomolecular Activity

Department: Department of Organic Chemistry, Faculty of Chemical Technology
Study programmes: Chemie, Chemistry
Theses supervisor: Mgr. Tomáš Slanina, Ph.D.

Annotation

The main objectives of the PhD project are the design, synthesis, spectroscopic characterization, development, and screening of various applications of the novel class of BODIPY-based photoremovable groups[1] and photoactivatable systems.[2] The main emphasis will be given to systems absorbing red light that can be activated in tissue transparent window[3]. Non-classical leaving groups, such as thiosufonates, xanthates, hydroxylamines, (thio)semicarbazones etc. will be combined with the BODIPY scaffold to produce systems releasing signaling molecules. The molecules will be also modified to produce biocompatible linkers that will be used for light-controlled modulation of biomolecular activity in optogenetic approach. The candidate will perform synthesis and characterization of organic photoactivatable molecules and will study their chemical, photophysical and photochemical properties. He/she will become a part of a dynamic junior research team investigating small organic molecules undergoing redox processes, photoactivatable compounds, and reversible chemical reactions. Highly motivated and skillful candidate will have the opportunity to extend his/her graduate training in physical and organic chemistry by learning electrochemical, photochemical and advanced spectroscopic methods.

Biological machine learning

Department: Department of Informatics and Chemistry, Faculty of Chemical Technology
Study programmes: Bioinformatika, Bioinformatics
Theses supervisor: Ing. Tomáš Pluskal, Ph.D.

Annotation

Our lab combines cutting-edge experimental (e.g., LC-MS, metabolomics, RNA-seq) and computational (e.g., bioinformatics, molecular networking, machine learning) approaches to develop rapid, generally applicable workflows for the discovery and utilization of bioactive molecules derived from plants. We are looking for talented and motivated computational researchers to join our team. The successful candidate for this position will be developing models for the prediction of enzymatic activities of enzymes in biosynthetic pathways. Owing to the interdisciplinary nature of the lab, this project will be conducted in close collaboration with experimental researchers who will be generating data for model training and verification.

Cathepsin proteases in biomedicine

Department: Department of Biochemistry and Microbiology, Faculty of Food and Biochemical Technology
Theses supervisor: RNDr. Michael Mareš, CSc.

Annotation

The project is focused on proteolytic enzymes of the cathepsin type that are critically involved in pathologies and are therapeutic targets. Cathepsins of human origin and those from pathogens and parasites will be investigated. The aim of the project is to analyze the structure and function of cathepsins and develop novel inhibitory molecules for their regulation. The research in the field of biochemistry and molecular biology employs the following main approaches: functional proteomics and chemical genomics, recombinant protein expression, enzymology, protein crystallography, and molecular modeling

Comprehensive approach to structural analysis of novel polycyclic diterpenes from termites

Department: Department of Organic Chemistry, Faculty of Chemical Technology
Study programmes: Chemie, Chemistry
Theses supervisor: Mgr. Pavlína Kyjaková, PhD.

Annotation

Termites are the group of insects with the richest repertoire of defensive chemicals. They are especially famous for the production of roughly one hundred different polycyclic diterpenes with variable topologies of double bonds combined with different oxygenated moieties attached to bi-, tri- and tetracyclic diterpene skeletons. In spite of the extensive quest for new termite diterpenes during the past decades, large part of their structural richness remains undiscovered. The proposed PhD. project focuses on chemical diversity of polycyclic diterpenes in the so-called Subulitermes group of species from South America, in which we recently unveiled an unexpected repertoire of diterpenes structures. The project will address the diterpene diversity as a tool for chemical taxonomy on the one hand, and an opportunity to fully identify structures of new and complex natural compounds on the other hand. The first goal will be to characterize individual species based on combination of characteristic chemical profiles with mitochondrial DNA sequences, to identify new species, to discriminate cryptic species, and ultimately to build phylogenetic hypotheses on their relationships. The knowledge on the overall diterpene diversity will serve as a basis for the second goal of the project, which will combine traditional analytical workflow with modern approaches and computational tools to fully characterize the molecular structures in a maximum of detected diterpenes.

Comprehensive approach to structural analysis of novel polycyclic diterpenes from termites

Department: Department of Chemistry of Natural Compounds, Faculty of Food and Biochemical Technology
Theses supervisor: Mgr. Pavlína Kyjaková, PhD.

Annotation

Termites are the group of insects with the richest repertoire of defensive chemicals. They are especially famous for the production of roughly one hundred different polycyclic diterpenes with variable topologies of double bonds combined with different oxygenated moieties attached to bi-, tri- and tetracyclic diterpene skeletons. In spite of the extensive quest for new termite diterpenes during the past decades, large part of their structural richness remains undiscovered. The proposed PhD. project focuses on chemical diversity of polycyclic diterpenes in the so-called Subulitermes group of species from South America, in which we recently unveiled an unexpected repertoire of diterpenes structures. The project will address the diterpene diversity as a tool for chemical taxonomy on the one hand, and an opportunity to fully identify structures of new and complex natural compounds on the other hand. The first goal will be to characterize individual species based on combination of characteristic chemical profiles with mitochondrial DNA sequences, to identify new species, to discriminate cryptic species, and ultimately to build phylogenetic hypotheses on their relationships. The knowledge on the overall diterpene diversity will serve as a basis for the second goal of the project, which will combine traditional analytical workflow with modern approaches and computational tools to fully characterize the molecular structures in a maximum of detected diterpenes.

Computational mass spectrometry

Department: Department of Informatics and Chemistry, Faculty of Chemical Technology
Study programmes: Bioinformatika, Bioinformatics
Theses supervisor: Ing. Tomáš Pluskal, Ph.D.

Annotation

Our lab combines cutting-edge experimental (e.g., LC-MS, metabolomics, RNA-seq) and computational (e.g., bioinformatics, molecular networking, machine learning) approaches to develop rapid, generally applicable workflows for the discovery and utilization of bioactive molecules derived from plants. We are looking for talented and motivated computational researchers to join our team. The successful candidate for this position will be developing the next generation of the MZmine platform (https://mzmine.github.io) for mass spectrometry data processing in metabolomics. Among other things, we are aiming to add full support for ion mobility spectroscopy (IMS) to MZmine, and to enhance its molecular networking capabilities. Experience with Java programming is recommended.

Crystalline sponge method

Department: Department of Chemistry of Natural Compounds, Faculty of Food and Biochemical Technology
Theses supervisor: Ing. Tomáš Pluskal, Ph.D.

Annotation

Our lab combines cutting-edge experimental (e.g., LC-MS, metabolomics, RNA-seq) and computational (e.g., bioinformatics, molecular networking, machine learning) approaches to develop rapid, generally applicable workflows for the discovery and utilization of bioactive molecules derived from plants. We are looking for talented and motivated chemist with a strong experience in small molecule X-ray crystallography. The successful candidate for this position will be developing protocols for the “crystalline sponge” structure elucidation method and applying them to various plant natural products, particularly terpenes.

Design and synthesis of inhibitors of purine nucleoside phosphorylases – SAR study

Department: Department of Organic Chemistry, Faculty of Chemical Technology
Study programmes: Chemie, Chemistry
Theses supervisor: Ing. Zlatko Janeba, Ph.D.

Annotation

We have recently prepared a novel type of acyclic nucleoside phosphonates as potent inhibitors of human purine nucleoside phosphorylase (hPNP). Such compounds may have potential to treat various T-cell leukemias. In order to select suitable candidates for preclinical evaluation, the goal is design and synthesis of a larger amount of derivatives and evaluation of their biological properties. The synthesis of potential PNP inhibitors will be developed and optimized.

Design and synthesis of inhibitors of purine nucleoside phosphorylases – SAR study

Department: Department of Chemistry of Natural Compounds, Faculty of Food and Biochemical Technology
Theses supervisor: Ing. Zlatko Janeba, Ph.D.

Annotation

We have recently prepared a novel type of acyclic nucleoside phosphonates as potent inhibitors of human purine nucleoside phosphorylase (hPNP). Such compounds may have potential to treat various T-cell leukemias. In order to select suitable candidates for preclinical evaluation, the goal is design and synthesis of a larger amount of derivatives and evaluation of their biological properties. The synthesis of potential PNP inhibitors will be developed and optimized.

Design and synthesis of novel photoswitches derived from heteroarylazobenzenes and bis-azobenzenes

Department: Department of Organic Chemistry, Faculty of Chemical Technology
Study programmes: Chemie, Chemistry
Theses supervisor: Ing. Zlatko Janeba, Ph.D.

Annotation

We have recently reported synthesis of variously substituted 5-phenylazopyrimidines (see references for more information). Their physicochemical properties were studied using in situ irradiation NMR spectroscopy and optical spectroscopy. The goal of the current project will be synthesis of novel molecular photoswitches based on a combination of bis-azobenzenes and pyrimidines (and other heterocycles), namely bis(pyrimidinyldiazenyl)benzenes. Their synthesis will be developed/optimized and their physicochemical properties will be studied.

Design and synthesis of novel photoswitches derived from heteroarylazobenzenes and bis-azobenzenes

Department: Department of Chemistry of Natural Compounds, Faculty of Food and Biochemical Technology
Theses supervisor: Ing. Zlatko Janeba, Ph.D.

Annotation

We have recently reported synthesis of variously substituted 5-phenylazopyrimidines (see references for more information). Their physicochemical properties were studied using in situ irradiation NMR spectroscopy and optical spectroscopy. The goal of the current project will be synthesis of novel molecular photoswitches based on a combination of bis-azobenzenes and pyrimidines (and other heterocycles), namely bis(pyrimidinyldiazenyl)benzenes. Their synthesis will be developed/optimized and their physicochemical properties will be studied.

Design and synthesis of novel prodrugs of acyclic nucleoside phosphonates

Department: Department of Organic Chemistry, Faculty of Chemical Technology
Study programmes: Chemie, Chemistry
Theses supervisor: Ing. Zlatko Janeba, Ph.D.

Annotation

Acyclic nucleoside phosphonates (ANPs) represent an important class of antiviral agents. The phosphonate group is deprotonated at physiological pH and, thus, ANPs are polar molecules unable to effectively penetrate into cells. Prodrugs of ANPs help to overcome this obstacle. The goal of the project will be design and synthesis of novel prodrugs of ANPs and study of their properties.

Design and synthesis of novel prodrugs of acyclic nucleoside phosphonates

Department: Department of Chemistry of Natural Compounds, Faculty of Food and Biochemical Technology
Theses supervisor: Ing. Zlatko Janeba, Ph.D.

Annotation

Acyclic nucleoside phosphonates (ANPs) represent an important class of antiviral agents. The phosphonate group is deprotonated at physiological pH and, thus, ANPs are polar molecules unable to effectively penetrate into cells. Prodrugs of ANPs help to overcome this obstacle. The goal of the project will be design and synthesis of novel prodrugs of ANPs and study of their properties.

Development of new chemical tools to study cell-cell interactions

Department: Department of Organic Chemistry, Faculty of Chemical Technology
Study programmes: Chemie, Chemistry
Theses supervisor: Ing. Milan Vrábel, Ph.D.

Annotation

Cell-cell interactions play an important role in a myriad of biological processes. These interactions enable cells to communicate, respond to changes in the environment and are involved in many pathologies including cancer. Despite their importance, our ability to study the molecular details and nature of these interactions is still very limited. In this project, we will employ chemical glycoengineering in combination with biocompatible chemical crosslinking reactions to capture, identify and study biomolecules involved in these interactions. This project aims to elucidate the complexity of cell-cell interactions and shed light on individual proteins involved in the process. The ideal candidate should have interest in organic chemistry, chemical biology and related fields.

Development of new chemical tools to study cell-cell interactions

Department: Department of Chemistry of Natural Compounds, Faculty of Food and Biochemical Technology
Theses supervisor: Ing. Milan Vrábel, Ph.D.

Annotation

Cell-cell interactions play an important role in a myriad of biological processes. These interactions enable cells to communicate, respond to changes in the environment and are involved in many pathologies including cancer. Despite their importance, our ability to study the molecular details and nature of these interactions is still very limited. In this project, we will employ chemical glycoengineering in combination with biocompatible chemical crosslinking reactions to capture, identify and study biomolecules involved in these interactions. This project aims to elucidate the complexity of cell-cell interactions and shed light on individual proteins involved in the process. The ideal candidate should have interest in organic chemistry, chemical biology and related fields.

Enantioselective catalysis under the control of helical chirality

Department: Department of Organic Chemistry, Faculty of Chemical Technology
Study programmes: Chemie, Chemistry
Theses supervisor: RNDr. Ivo Starý, CSc.

Annotation

The goal of the PhD project will be the development of new helically chiral ligands and metal complexes to be explored in enantioselective catalysis. The attention will be paid to asymmetric synthesis of helicene-derived N-heterocyclic carbenes, cyclic (alkyl)(amino)carbenes and cyclometallated helicenes. These chiral ligands/metal complexes will be applied to selected enantioselective reactions catalysed by transition metals such as alkyne cycloisomerisation, olefin metathesis or hydrogenation.

Modified DNAzymes and DNA origami

Department: Department of Organic Chemistry, Faculty of Chemical Technology
Study programmes: Chemie, Chemistry
Theses supervisor: prof. Ing. Michal Hocek, DSc.

Annotation

We will design and synthesize modified deoxyribonucleoside triphosphates bearing functional groups or ligands for complexation of metals. They will be used for enzymatic synthesis of modified oligonucleotides which will be applied in selection and construction of functional DNAzymes or DNA origami.

Modified DNAzymes and DNA origami

Department: Department of Chemistry of Natural Compounds, Faculty of Food and Biochemical Technology
Theses supervisor: prof. Ing. Michal Hocek, DSc.

Annotation

We will design and synthesize modified deoxyribonucleoside triphosphates bearing functional groups or ligands for complexation of metals. They will be used for enzymatic synthesis of modified oligonucleotides which will be applied in selection and construction of functional DNAzymes or DNA origami.

New deazapurine nucleosides and nucleotides as potential antivirals or cytostatics

Department: Department of Organic Chemistry, Faculty of Chemical Technology
Study programmes: Chemie, Chemistry
Theses supervisor: prof. Ing. Michal Hocek, DSc.

Annotation

The recently reported synthesis of perfluoroalkyl azides and triazoles1 opened the door to study properties and reactivity of these compounds. In this project, the rich chemistry of (per)fluoroalkyl azides and triazoles1-10 will be investigated and new synthetic approaches to underdeveloped N-fluoroalkyl-containing compounds such as azides, azoles, azirines, ureas, carbamates, and amides will be studied. This class of compounds is expected to find utilization in drug discovery and in the development of new materials

New deazapurine nucleosides and nucleotides as potential antivirals or cytostatics

Department: Department of Chemistry of Natural Compounds, Faculty of Food and Biochemical Technology
Theses supervisor: prof. Ing. Michal Hocek, DSc.

Annotation

We will design and synthesize new modified deazapurine nucleosides, nucleotides and prodrugs as inhibitors of polymerases or other enzymes of nucleotide metabolism, or as ligands (agonists or antagonists) of nucleotide receptors. Selected active compounds will be further optimized in order to identify preclinical candidates for development of potential antiviral or antitumour agents.

New heterocyclic inhibitors of selected protein kinases

Department: Department of Organic Chemistry, Faculty of Chemical Technology
Study programmes: Chemie, Chemistry
Theses supervisor: prof. Ing. Michal Hocek, DSc.

Annotation

We will design and synthesize modified heterocyclic compounds as inhibitors of selected protein kinases that are relevant targets for potential therapeutics of tumours or neurodegenerative diseases. A combination of rational design, synthesis of combinatorial libraries and optimization of hits will be used.

New heterocyclic inhibitors of selected protein kinases

Department: Department of Chemistry of Natural Compounds, Faculty of Food and Biochemical Technology
Theses supervisor: prof. Ing. Michal Hocek, DSc.

Annotation

We will design and synthesize modified heterocyclic compounds as inhibitors of selected protein kinases that are relevant targets for potential therapeutics of tumours or neurodegenerative diseases. A combination of rational design, synthesis of combinatorial libraries and optimization of hits will be used.

Nonplanar unconventional pi-electron systems

Department: Department of Organic Chemistry, Faculty of Chemical Technology
Study programmes: Chemie, Chemistry
Theses supervisor: RNDr. Irena Stará, CSc.

Annotation

The project is focused on the synthesis of extended (hetero)helicenes, bi(hetero)helicenes and (hetero)cycloarenes. In particular, the attention will be paid to chiroptical switches (based on exciton coupling), single-molecule electromechanical properties and charge transport in thin layers. Chirality issues will be central to all endeavours. A concept of the covalent template synthesis of pi-conjugated macrocycles will be explored.

Role of adhesion-GPCRs during viral infection of mammalian cells

Department: Department of Biochemistry and Microbiology, Faculty of Food and Biochemical Technology
Theses supervisor: Mgr. Jan Weber, CSc.

Annotation

The proposed PhD project addresses the possible role of adhesion G protein-coupled receptors (aGPCRs) during viral infection of mammalian cells. The aGPCRs are intriguing class of seven-transmembrane proteins that play important role in neurodevelopment, immune defense and cancer, but their role during viral infection is mostly unexplored. Currently, we recognize 33 members of aGPCRs in humans but majority are orphan receptors with unknown function. We intend to search for specific aGPCR and/or cellular proteins in aGPCRs pathways involved in infections of mammalian cells and characterize their interaction with viral proteins. During postgradual study, student will learn how to work with cell cultures in biosafety level 3, perform proteomic and bioinformatic analyses and siRNA experiments for gene-knockdown in mammalian cells infected with various viruses. Proposed project will broaden our current knowledge about the role of aGPCRs in infections of mammalian cells and if successful, it can identify potential targets for antiviral therapy.

Structure of carbohydrates investigated by NMR spectroscopy and molecular modeling

Department: Department of Analytical Chemistry, Faculty of Chemical Engineering
Theses supervisor: Ing. Radek Pohl, Ph.D.

Annotation

Carbohydrates are the most abundant biomolecules with enormous structural diversity. They are present in the Nature in the form of mono-, di-, oligo- or polysaccharides but also as a part of glycoconjugates such as glycoproteins, peptidoglycans or glycolipids. Consequently, this structural variety makes carbohydrates the least exploited among biomolecules. In addition to the structural diversity, originating from multi-linkage and branching of monosaccharides, carbohydrates are usually flexible molecules that can exist in various conformations. All this makes structural studies of carbohydrates difficult and challenging.
NMR spectroscopy is, among other experimental techniques, the most exploited method in determination of carbohydrate structure. The advantage of NMR is the possibility to study molecules of interest in both solution and solid state and at the same time correlate multiple parameters (chemical shift, coupling constants, NOE, relaxation times) with the structure. On the other hand, NMR spectra of carbohydrates are complex due to significant signal overlap and averaging of NMR parameters in solution experiments. Many NMR parameters respond sensitively to changes in structure, which is however not directly deducible from NMR spectra. Therefore, a combination of experimental NMR with molecular modeling techniques is frequently used in carbohydrate structure determination.
The aim of the PhD project is studying of carbohydrate structures by NMR spectroscopy and explore various NMR techniques in combination with molecular modelling that can be used in order to fulfil this task. Particular emphasis will be given to the sensitivity of NMR parameters to conformational changes and to the influence of the environment on carbohydrate structure. The studied compounds will be synthesized in a collaborating laboratory of Dr. Kamil Parkan at UCT Prague.

Synthesis and application of N-fluoroalkylated compounds

Department: Department of Organic Chemistry, Faculty of Chemical Technology
Study programmes: Chemie, Chemistry
Theses supervisor: Ing. Petr Beier, Ph.D.

Annotation

The recently reported synthesis of perfluoroalkyl azides and triazoles1 opened the door to study properties and reactivity of these compounds. In this project, the rich chemistry of (per)fluoroalkyl azides and triazoles1-10 will be investigated and new synthetic approaches to underdeveloped N-fluoroalkyl-containing compounds such as azides, azoles, azirines, ureas, carbamates, and amides will be studied. This class of compounds is expected to find utilization in drug discovery and in the development of new materials

The development and application of organelle-targeted bioorthogonal cleavage reactions

Department: Department of Organic Chemistry, Faculty of Chemical Technology
Study programmes: Chemie, Chemistry
Theses supervisor: Ing. Milan Vrábel, Ph.D.

Annotation

Chemical reactions that can be performed under physiological conditions offer unique possibility to manipulate and study biological processes. Our group has a long-term interest in these, so-called, bioorthogonal reactions. They are mainly known as efficient chemical transformations leading to formation of covalent bonds. It has been only recently when the concept was extended to something what is known as bioorthogonal cleavage reactions. The power of this type of reactions is only slowly becoming recognized. In this project, we aim to develop and employ the release reactions, which will enable de-caging of small molecules within specific cellular compartments. We believe that such systems will offer not only a unique possibility to deliver and activate functional molecules within particular subcellular location, but in a broader sense, to shed light on the function of individual cellular organelles. This project combines organic chemistry with modern chemical biology experiments.

The development and application of organelle-targeted bioorthogonal cleavage reactions

Department: Department of Chemistry of Natural Compounds, Faculty of Food and Biochemical Technology
Theses supervisor: Ing. Milan Vrábel, Ph.D.

Annotation

Chemical reactions that can be performed under physiological conditions offer unique possibility to manipulate and study biological processes. Our group has a long-term interest in these, so-called, bioorthogonal reactions. They are mainly known as efficient chemical transformations leading to formation of covalent bonds. It has been only recently when the concept was extended to something what is known as bioorthogonal cleavage reactions. The power of this type of reactions is only slowly becoming recognized. In this project, we aim to develop and employ the release reactions, which will enable de-caging of small molecules within specific cellular compartments. We believe that such systems will offer not only a unique possibility to deliver and activate functional molecules within particular subcellular location, but in a broader sense, to shed light on the function of individual cellular organelles. This project combines organic chemistry with modern chemical biology experiments.

The mannose-6-phosphate/insulin-like growth factor 2 receptor as a target for memory enhancement and tumor suppression

Department: Department of Biochemistry and Microbiology, Faculty of Food and Biochemical Technology
Theses supervisor: RNDr. Lenka Žáková, Ph.D.

Annotation

Identifying new compounds that effectively improve neurodegenerative disease is an urgent need. It has been recently shown that insulin-like growth factor 2 (IGF2) has an important role in enhancement of memory. IGF2 is a fetal growth factor that has also significant role in mature mammalian brain. The effect of IGF2 as a cognitive enhancer is rapid and persistent, and is mediated by mannose-6-phosphate/IGF2 receptor (M6P/IGF2R). M6P/IGF2R is a large transmembrane glycoprotein that except IGF2 can bind M6P-containing ligands and binding of one ligand may affect the binding another one. Moreover, overexpression of IGF2 plays important role in development of certain tumors and M6P/IGF2R can play a role as a tumor suppressor. This project is focused on (i) production of M6P/IGF2R or its constructs, (ii) preparation of IGF2R selective IGF2 analogues, and (iii) a libraries of small molecule compounds. This work should lead to important clinical applications of new IGF2 analogues.


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