Improved Physical Stability of an Antibody-Drug Conjugate Using Host-Guest Chemistry
| Autor: | Conor S. Barry, Balakumar Vijayakrishnan, Maria Laura Greco, Christopher F. van der Walle, Howard Phillip Wilson, Silvia Sonzini, Thais Cailleau, Peter Ravn, Luke Masterson, Lauren Adams |
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| Rok vydání: | 2019 |
| Předmět: |
Bridged-Ring Compounds
Antibody-drug conjugate Immunoconjugates Biomedical Engineering Supramolecular chemistry Pharmaceutical Science Pyrrolobenzodiazepine Bioengineering 010402 general chemistry 01 natural sciences Polyethylene Glycols 03 medical and health sciences chemistry.chemical_compound Benzodiazepines 0302 clinical medicine Drug Stability Moiety Pyrroles Host–guest chemistry Pharmacology Indole test Chemistry Organic Chemistry Imidazoles Chemical modification Combinatorial chemistry 3. Good health 0104 chemical sciences body regions 030220 oncology & carcinogenesis Hydrophobic and Hydrophilic Interactions Biotechnology Conjugate |
| Zdroj: | Sonzini, S, Greco, M L, Cailleau, T, Adams, L, Masterson, L, Vijayakrishnan, B, Barry, C, Howard, P, Ravn, P & Van Der Walle, C F 2020, ' Improved Physical Stability of an Antibody–Drug Conjugate Using Host–Guest Chemistry ', Bioconjugate Chemistry, vol. 31, no. 1, pp. 123-129 . https://doi.org/10.1021/acs.bioconjchem.9b00809 Bioconjugate Chemistry |
| ISSN: | 1520-4812 |
| DOI: | 10.1021/acs.bioconjchem.9b00809 |
| Popis: | Antibody-drug conjugates (ADCs) are an emerging class of biopharmaceutical products for oncology, with the cytotoxic pyrrolobenzodiazepine (PBD) family of "warheads" well-established in the clinic. While PBDs offer high potency, they are also characterized by their hydrophobicity, which can make formulation of the ADC challenging. Several approaches have been investigated to improve the physicochemical properties of PBD-containing ADCs, and herein a supramolecular approach was explored using cucurbit[8]uril (CB[8]). The ability of CB[8] to simultaneously encapsulate two guests was exploited to incorporate a 12-mer polyethylene glycol harboring a methyl viologen moiety at one terminus (MV-PEG12), together with a PBD harboring an indole moiety at the C2' position (SG3811). This formulation approach successfully introduced a hydrophilic PEG to mask the hydrophobicity of SG3811, improving the physical stability of the ADC while avoiding any loss of potency related to chemical modification. |
| Databáze: | OpenAIRE |
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