Non-aromatic Heterocyclization-based DNA-encoded Glycan Library (DEGL)
Overview of DNA-encoded Glycan Library (DEGL)
DEGLs offer a novel approach for the rapid and efficient identification of glycans for targeted proteins. These libraries consist of organic molecules covalently linked to unique DNA tags, which act as amplifiable identification barcodes. The use of DNA encoding allows for in vitro ligand selection through affinity capture at sub-picomolar concentrations for virtually any target protein, akin to established methods such as antibody phage display. CD BioGlyco has explored numerous strategies to construct DEGLs, potentially containing millions of DNA-encoded glycan compounds. Besides, our next-generation high-throughput sequencing has facilitated the swift identification of binding molecules from DNA-encoded libraries (DELs).
DEGL: Revolutionizing Glycan Research with Non-aromatic Heterocyclization
Identifying specific binding molecules poses a fundamental challenge in chemistry, biology, and medicine. Therefore, CD BioGlyco is pleased to provide DEGL construction service that is based on sophisticated non-aromatic heterocyclization. Our service aims to advance ligand discovery, which could significantly enhance the understanding of biological mechanisms and accelerate drug development. Our researchers use the latest knowledge and developments in non-aromatic heterocyclization reactions, substantially expanding the horizons of glycan library construction by integrating compounds with enhanced sp3 hybridization. These advanced compounds address the limitations inherent in planar aromatic heterocycles, thereby augmenting the bioactivity potential of drug-like entities. We possess the ability to tailor custom DEGL solutions according to the specific requirements of our clients. Our research team will help clients to create DEGL that includes hundreds of thousands of DNA-encoded glycan molecules to ensure a vast array of chemical diversity tailored to meet the unique needs of each project by employing a suite of state-of-the-art techniques.
Monocyclic Non-aromatic Heterocyclizations
- Five-membered non-aromatic heterocycles: We focus on the on-DNA synthesis of glycans featuring monocyclic non-aromatic heterocycle structures. This includes oxazolidinones, which are synthesized from epoxides and primary amines; imidazolidinones, derived from amino acids and aldehydes; and isoindolinones, created from amides and bromomethylbenzoates.
- α, β-Unsaturated ketone heterocyclizations: Our offerings extend to the transformation of DNA-linked α, β-unsaturated ketones into isoxazolines via hydroxylamine, pyrazolines through hydrazine, and pyrrolidines via 1,3-dipolar cycloaddition reactions, thus broadening the chemical diversity of the library.
- Six-membered non-aromatic heterocycles: We employ stannyl amino protocol reactions for the efficient creation of six-membered rings, such as piperazines and morpholines, as well as morpholinones, pyridinones, and pyrimidinones, all achieved through on-DNA methods.
Polycyclic Non-aromatic Heterocycles
Our research team also synthesizes intricate polycyclic structures like β-carbolines, isoquinolones, and tetrahydroquinolines, utilizing Pictet-Spengler and Povarov reactions to enrich the chemical variety within glycan libraries.
Spirocyclic Compound
In addition, advanced spirocyclization techniques are employed, including the application of tertiary amine effects and au(I)-catalyzed multicomponent reactions to generate spirocyclic compounds such as 6-oxa-1,2-diazaspiro[4.4]nonanes.
The sophisticated technologies we use ensure that all chemical reactions are compatible with DNA.
Workflow
The steps for constructing DGELs using non-aromatic heterocyclization are as follows:
The First Cycle
The synthesis begins with the preparation of some distinct initial compounds. These compounds are coupled with an amino-labeled oligonucleotide carrying Encoding 1 via amide bond formation, resulting in a series of initial conjugates. These initial conjugates are then mixed.
Non-aromatic Heterocyclization
Next, non-aromatic heterocyclization is carried out using hundreds of different glycan derivatives. In this step, each initial conjugate reacts with each of the glycan derivatives, theoretically yielding a mass of distinct products.
The Second Cycle
To encode and distinguish the reaction products, a DNA polymerase-mediated hybridization and filling reaction is employed. Oligonucleotide segments carrying Encoding 2 are added to each reaction system. This step utilizes DNA hybridization and extension reactions, assigning a unique DNA tag (a combination of Encoding 1 and Encoding 2) to each reaction product, thus facilitating the tracking and identification of each compound.
Product Mixing and Library Formation
Finally, all reaction products are mixed to create a DNA-encoded chemical library with a large number of unique glycans. The quantity can be adjusted to meet the client's requirements, with options available for one hundred thousand, one million, or even ten million units. Each member of this library can be identified and selected via its unique DNA tag, thereby aiding in subsequent screening, analysis, and applications.
In summary, this process leverages the encoding capability of DNA and the efficiency of the non-aromatic heterocyclization reaction to build a large-scale and structurally diverse glycan library, providing a powerful tool for drug discovery, materials science, and other research areas.
Publication Data
Technology: Pharmacokinetic, Toxicological, Drug design, Drug discovery
DOI: 10.3390/pharmaceutics15112554
Journal: Pharmaceutics
Published: 2023
IF: 4.9
Results: The review extensively examines the most effective five-membered non-aromatic heterocycles utilized in the development of essential antibacterial medications. The authors underscore the importance of understanding and optimizing the intrinsic properties of these heterocycles to advance the creation of antibacterial drugs with improved efficacy, pharmacokinetic profiles, and safety. The design of antibacterial compounds is heavily reliant on the incorporation of heterocycles. Integrating five-membered non-aromatic heterocycles into drug molecules offers the potential for enhancing the antibacterial efficacy of these agents. These non-aromatic heterocyclic structures introduce pivotal structural elements that facilitate interactions with specific bacterial targets, potentially augmenting the effectiveness of antibacterial treatments. The study enumerates various categories of antibacterial agents, some of which incorporate one or more five-membered non-aromatic heterocycles in their molecular frameworks, such as oxazolidinones and imidazolidinone. The manuscript emphasizes the crucial role of the physicochemical properties of five-membered heterocycles in shaping the biological activity of antibacterial drugs. These properties influence not only the spectrum of activity and potency of the drugs but also their pharmacokinetic, pharmacological, and toxicological profiles. The dimensions and configuration of the heterocycles can affect their interaction with bacterial enzymes, thereby modulating efficacy against various bacteria. Additionally, the presence of specific functional groups on these heterocycles can impact their ability to traverse bacterial cell membranes, thus influencing their overall activity spectrum.
Applications
- DEGLs act as a formidable asset in the realm of drug discovery, significantly contributing to the process of pinpointing novel pharmaceutical compounds through the prediction of their biological activity and potential interactions.
- DEGLs can be used to explore the interplays between carbohydrate polymers and biological entities such as proteins and cellular components, uncovering the enigmas of life's operations.
- DEGLs are useful for the synthesis of cutting-edge functional materials, including biosensors and drug delivery systems.
Advantages of Us
- Our researchers employ optimized reaction conditions and efficient catalyst systems to efficiently and precisely construct glycan with non-aromatic heterocyclic structures on DNA.
- Our research team constructs a diverse range of non-aromatic heterocyclic glycan libraries by designing different reaction pathways and substrate combinations, catering to various research needs.
- We possess the ability to build a large-scale and structurally diverse glycan library that provides a powerful tool for drug discovery, materials science, and other research areas.
Frequently Asked Questions
- During the library synthesis process, which strategies are also utilized?
- How is our service process carried out?
- Demand communication: Engage in comprehensive discussions with clients to elucidate research goals and specific requirements.
- Scheme design: Develop an optimal synthesis plan tailored to the client's needs and perform an initial evaluation.
- Experiment execution: Carry out the synthesis plan under stringent laboratory conditions, implementing necessary adjustments.
- Quality control: Execute meticulous quality assurance checks on each reaction product to ensure the construction of a high-quality glycan library.
- Data delivery: Compile and organize experimental findings, craft a thorough report, and provide it to the client.
CD BioGlyco's DEGL construction utilizes advanced chemical synthesis techniques to intricately integrate a diverse range of glycan with non-aromatic heterocyclic structures directly onto DNA strands. These structures, characterized by their prominent sp3 hybridization, represent a pioneering advancement in glycoscience and pharmaceutical research, significantly expanding the capabilities of traditional DELs. If you want to surpass conventional constraints, contact us, we will offer a vast chemical diversity and broadening the utility of glycan compounds across various scientific fields for you.
Reference
- Rusu, A.; et al. The role of five-membered heterocycles in the molecular structure of antibacterial drugs used in therapy. Pharmaceutics. 2023, 15(11): 2554.
For research use only. Not intended for any clinical use.
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