DOTAGA Chelating Peptide Synthesis

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As a leading biopharmaceutical company, Creative Peptides are pioneering new pathways in the synthesis of DOTAGA chelating peptides. Our commitment to providing this cutting-edge prescribing product reflects our dedication to advancing the field of biomedical research and employing sophisticated and diverse modalities in the creation of advanced medical solutions.

What are DOTAGA chelating peptides?

DOTAGA (1,4,7,10-tetraazacyclododecane-1-glutaric acid-4,7,10-triacetic acid) is a macrocyclic compound used in bioconjugation chemistry. It is an analogue of DOTA. As a multifunctional chelating agent, it can form stable complexes with various metal ions, such as radionuclides.

DOTAGA chelating peptides are molecules designed to form strong and stable complexes with certain metal ions. These polymers are especially useful in the field of medicine for targeted drug delivery, diagnostic imaging, and in the development of theranostic agents. They are often conjugated to antibodies, peptides, or other biological molecules to achieve targeted delivery to specific cells or tissues in the body.

After DOTAGA is combined with peptide, radioisotopes can be introduced into peptide molecules, so that peptide can be used to label and track biomolecules, study biological processes or treat diseases. At the same time, DOTAGA is usually very stable, which can maintain its structure in vivo and ensure that radioisotopes will not be released into surrounding tissues, which is very important for imaging and therapeutic applications.

Advantages of DOTAGA chelating peptide

High stability: The chelates formed by DOTAGA and metal ions have excellent stability, which enables DOTAGA chelated peptides to maintain their structure and function for a long time in vivo environment, ensuring efficient and lasting effects on specific targets.

Specific binding: It has high specificity and affinity for certain metal ions, particularly lanthanides. This makes it a viable medical tool for applications such as diagnostic imaging and therapy.

Strong chelating ability: DOTAGA, as a strong chelating agent, can form stable complexes with various metal ions. This characteristic makes DOTAGA chelate peptide have a wide application prospect in the fields of radiopharmaceutical preparation and nuclear magnetic resonance imaging.

Good biocompatibility: DOTAGA chelating peptide has good compatibility with organisms, which can reduce immunogenicity and reduce the occurrence of adverse reactions. This makes it safer and more reliable in vivo application.

Targeting: By modifying the peptide, DOTAGA chelating peptide can accurately target specific biomolecules or cells. This targeting enables drugs to act more directly on the lesion, improving the therapeutic effect and reducing side effects.

Increase diagnostic accuracy: It can significantly enhance the contrast of magnetic resonance imaging (MRI), resulting in clearer and more precise diagnostic images.

Applications of DOTAGA chelating peptide

Medical imaging: DOTAGA chelating peptides can be used to create contrast agents for magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging. They are used to chelate or bind to radioactive metals that can be detected by these imaging techniques.

Drug delivery: They can be used to target and deliver drugs selectively to certain cells or tissues. This allows for more efficient drug delivery, reducing side effects and increasing efficacy.

Cancer treatment: They are researched for their potential applications in cancer therapy. For instance, they can be used in radioimmunotherapy where a DOTAGA chelating peptide conjugated to an antibody targets specific cancer cells, and the radioactive metal emits radiation that kills the cancer cells.

Cell tracking: They can be used to track the migration and differentiation of stem cells and other cellular therapeutic agents in the body.

Engineering of radioactive drugs: In pharmaceutical drug development, DOTAGA chelating peptides can be incorporated in the formulation of some drugs, particularly radioactive drugs. This helps to stabilize the radioactive isotopes that are integral to the function of these medications.

Research and development: They are used in various scientific research to study cell interaction, cell death, tissue regeneration and other biological processes. They also serve as a helpful tool in pharmaceutical research and development.

Integrin αvβ3 receptor targeting peptide ligand, internalizing Arg-Gly-Asp (iRGD), exhibits intrinsiccharacteristic of cellular internalization and thereby promotes tumortissue penetration of imaging agents, drugs, dyes, and nanoparticles. Higher imaging sensitivity and enhanced therapeutic efficacy can thus be achieved through iRGD peptide conjugates. By introducing a bifunctional chelating agent related to DOTAGA, iRGD peptide for tumor localization was synthesized. This peptide was modified to form ⁶⁸Ga-DOTAGA-iRGD, and this radiolabeled iRGD peptide was used for visualization or treatment of cancer sites. Ga (III) cation coordinates with four nitrogen atoms and two carboxyl groups in ⁶⁸Ga-DOTAGA-iRGD chelate, thus forming a hexacoordinated octahedral structure. A carboxyl group of the ⁶⁸Ga-DOTAGA complex forms a peptide bond, so a negative charge is generated in the ⁶⁸Ga-DOTAGA complex. Then, the biological distribution, clearance characteristics and tumor uptake of ⁶⁸Ga-DiRGD were studied and compared with ⁶⁸Ga-NiRGD. It was found that ⁶⁸Ga-DiRGD modified by DOTAGA was more hydrophilic than ⁶⁸Ga-NiRGD, and showed higher penetration of tumor tissue and faster clearance rate from blood, liver and intestine. And DOTAGA has an edge over NODAGA as it forms stable complexes with therapeutic radionuclides (⁹⁰Y/¹⁷⁷Lu) and thus can be translated for preparation of therapeutic radiopharmaceuticals.

Fig. 1 Schematic representation of structures of ⁶⁸Ga-DiRGD and ⁶⁸Ga-NiRGD. (Satpati, D., 2020)

Our services

• Synthesis of DOTAGA chelating peptide: ~8000 Da

Fig. 2 Schematic diagram of DOTAGA chelating peptide.

1. Peptides Linker 1 and Linker 2 were successfully synthesized by the strategy of "three-side chain synchronous modification"

2. Several tert-butyl groups of DOTAGA on linker1 were successfully removed, and linker2 with better purity was obtained by purification

3. Triazole linkers were successfully synthesized between Linker 1 and Linker 2 by click chemistry

4. The product with HPLC purity over 95% was successfully obtained

• DOTA-Mal: It can be bonded to the peptide with SH through Maleimide (MAL), and the amino acid with sulfhydryl in the peptide is Cys, or by introducing SH, such as mercaptoacetic acid and mercaptopropionic acid.
• Butyne-DOTA-tris(t-butyl ester): Click Reaction occurs between alkynes and amino acids with N3, and amino acids with sulfhydryl groups in peptides are Lys(N3), or by introducing N3, such as azidoacetic acid and azidopropionic acid.
• Mono-amide-DOTA: Dota modification of peptide is completed by chelating NH₂ bond on benzene ring and amino acid with COOH.
• Bn-SCN-DOTA: SCN isothiocyanate can be added to amino acid with NH₂ to complete DOTA modification of peptide.
• N3-DOTA-tBu: Click Reaction occurs with amino acids with alkynes through N3, and amino acids with sulfhydryl groups in the peptide are alkynyl propionic acid, or by introducing alkynyl groups, such as alkynyl butyric acid and alkynyl valeric acid.
• DOTA(tBu)-COOH: DOTA modification of peptide is completed by chelating agent COOH bond and amino acid with NH₂.
• HYNIC, DTPA, DOTA, NOTA and their derivatives modified peptides.

Fig. 3 Other common DOTA chelating agents.

Our advantages

Industry-leading expertise: Our team comprises of highly trained professionals with industry-leading expertise in biochemical synthesis. We are renowned for synthesizing DOTAGA chelating peptides with high level of precision.

Advanced technology: We utilize the latest technology in peptide synthesis to provide reliable and efficient service to our clients. This allows us to maintain a high level of consistency and precision in our results.

Quality assurance: We are committed to maintaining high-quality standards. Our processes are rigorously tested to ensure that the final product meets the required specifications.

Customized solutions: Understanding your specific needs, we offer customized solutions to meet your objectives. Each project is handled individually to make sure it meets the distinct needs of our clients.

Comprehensive services: We offer comprehensive services in DOTAGA chelating peptide synthesis, from design and production, to purification and characterization. This saves our clients' time and hassle of coordinating with multiple service providers.

Speedy turnaround: We understand the importance of time in your project pipeline. Striving to minimize production time, we offer a speedy turnaround time without compromising on the quality.

Confidentiality and data protection: We respect the confidentiality of our clients' data and have strict data protection policies in place.

Competitive pricing: Despite our superior services, we offer competitive pricing structure to provide a cost-effective solution to our clients.

Global reach: Regardless of your geographical location, we can serve you. We have a strong global presence and can deliver our services to clients all around the world.

Exceptional customer service: We understand the value of customer satisfaction and ensure seamless communication and top-notch customer service for all our clients.

FAQ

1. What exactly is DOTAGA chelating peptide synthesis?

DOTAGA chelating peptide synthesis involves the incorporation of the chelator DOTAGA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) into peptides in order to facilitate the binding and visualization of radionuclides. This process is most commonly used in radiopharmaceuticals for diagnostic imaging and therapeutic purposes.

2. What types of radiopharmaceuticals can be produced using DOTAGA chelating peptide synthesis?

Our service can be utilized to produce a wide range of radiopharmaceuticals. The resulting products are often used in nuclear medicine for the diagnosis or treatment of various diseases, including different types of cancer.

3. How long does the DOTAGA chelation process typically take?

The time taken for the DOTAGA chelation process may vary depending on the complexity of the peptide or protein to be chelated. However, our team of highly skilled professionals are dedicated to delivering the best results in a timely and efficient manner.

4. What quality control measures are in place to ensure the integrity of the resultant DOTAGA chelated peptides?

We have stringent quality control processes in place. These include HPLC analysis to verify the successful incorporation of DOTAGA into the peptide/protein and mass spectrometry to assess the integrity of the final product.

5. Can I order customized synthesis of a DOTAGA chelated peptide?

Yes, we provide customized solutions depending on the specific needs of the client. This includes assistance with peptide design, DOTAGA conjugation, purification, and quality control.

Reference

1. Satpati, D., et al. 68Ga-labeling of internalizing RGD (iRGD) peptide functionalized with DOTAGA and NODAGA chelators. Journal of Peptide Science. 2020, 26(3): e3241.