期刊
CHEMICAL SCIENCE
卷 4, 期 1, 页码 297-302出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c2sc21107f
关键词
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资金
- ETH Zurich
- Swiss National Science Foundation
- SwissBridge/Stammbach Stiftung
- Kommission fur Technologie und Innovation (KTI)
- Philochem AG
- Philogen SpA
We systematically investigated how the therapeutic efficacy of a traceless, vascular targeting antibody-drug conjugate (ADC) is affected by the length of a spacer introduced between the antibody's globular fold and the site of drug attachment. Homogeneous ADCs were prepared from the direct conjugation of engineered C-terminal cysteines with a potent thiol containing drug which was separated from the antibody surface by unstructured spacers of increasing length. We found that a smaller spacer length is reflected in enhanced stability and therapeutic efficacy of the conjugates in a syngeneic model of murine cancer.
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