RGD Peptidomimetic MMAE‐Conjugate Addressing Integrin αVβ3‐Expressing Cells with High Targeting Index**

Paulus J, Nachtigall B, Meyer P, Sewald N (2022)
Chemistry – A European Journal: e202203476.

Zeitschriftenaufsatz | E-Veröff. vor dem Druck | Englisch
 
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Abstract / Bemerkung
Small molecule-drug conjugates (SMDCs) mimicking the RGD sequence (-Arg-Gly-Asp-) with a non-peptide moiety require a pharmacophore-independent attachment site. A library of 36 sulfonamide-modified RGD mimetics with nM to pM affinity for integrin αVβ3 was synthesized and analysed via DAD mapping. The best structure of the conjugable RGD mimetic was used and a linker was attached to an aromatic ring by Negishi cross-coupling. The product retained high affinity and selectivity for integrin αVβ3. The conjugable RGD mimetic was then attached to an enzymatically cleavable GKGEVA linker equipped with a self-immolative PABC and the antimitotic drug monomethyl auristatin E (MMAE). The resulting SMDC preferred binding to integrin αVβ3 over α5β1 in a ratio of 1 : 4519 (ELISA) and showed selectivity for αVβ3-positive WM115 cells over αVβ3-negative M21-L cells in the in vitro cell adhesion assay as well as in cell viability assays with a targeting index of 134 (M21-L/WM115).
Erscheinungsjahr
2022
Zeitschriftentitel
Chemistry – A European Journal
Art.-Nr.
e202203476
ISSN
0947-6539
eISSN
1521-3765
Finanzierungs-Informationen
Open-Access-Publikationskosten wurden durch die Universität Bielefeld im Rahmen des DEAL-Vertrags gefördert.
Page URI
https://pub.uni-bielefeld.de/record/2967376

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Paulus J, Nachtigall B, Meyer P, Sewald N. RGD Peptidomimetic MMAE‐Conjugate Addressing Integrin αVβ3‐Expressing Cells with High Targeting Index**. Chemistry – A European Journal. 2022: e202203476.
Paulus, J., Nachtigall, B., Meyer, P., & Sewald, N. (2022). RGD Peptidomimetic MMAE‐Conjugate Addressing Integrin αVβ3‐Expressing Cells with High Targeting Index**. Chemistry – A European Journal, e202203476. https://doi.org/10.1002/chem.202203476
Paulus, Jannik, Nachtigall, Beate, Meyer, Peter, and Sewald, Norbert. 2022. “RGD Peptidomimetic MMAE‐Conjugate Addressing Integrin αVβ3‐Expressing Cells with High Targeting Index**”. Chemistry – A European Journal: e202203476.
Paulus, J., Nachtigall, B., Meyer, P., and Sewald, N. (2022). RGD Peptidomimetic MMAE‐Conjugate Addressing Integrin αVβ3‐Expressing Cells with High Targeting Index**. Chemistry – A European Journal:e202203476.
Paulus, J., et al., 2022. RGD Peptidomimetic MMAE‐Conjugate Addressing Integrin αVβ3‐Expressing Cells with High Targeting Index**. Chemistry – A European Journal, : e202203476.
J. Paulus, et al., “RGD Peptidomimetic MMAE‐Conjugate Addressing Integrin αVβ3‐Expressing Cells with High Targeting Index**”, Chemistry – A European Journal, 2022, : e202203476.
Paulus, J., Nachtigall, B., Meyer, P., Sewald, N.: RGD Peptidomimetic MMAE‐Conjugate Addressing Integrin αVβ3‐Expressing Cells with High Targeting Index**. Chemistry – A European Journal. : e202203476 (2022).
Paulus, Jannik, Nachtigall, Beate, Meyer, Peter, and Sewald, Norbert. “RGD Peptidomimetic MMAE‐Conjugate Addressing Integrin αVβ3‐Expressing Cells with High Targeting Index**”. Chemistry – A European Journal (2022): e202203476.
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2024-01-22T11:23:19Z
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