Conjugates of a Novel 7-Substituted Camptothecin with RGD-Peptides as [alpha]^sub v^[Beta]^sub 3^ Integrin Ligands: An Approach to Tumor-Targeted Therapy
Eight conjugates of a novel camptothecin derivative (Namitecan, NMT) with RGD peptides have been synthesized and biologically evaluated. This study focused on factors that optimize the drug linkage to the transport vector. The different linkages investigated consist of heterofunctional glycol fragme...
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| Veröffentlicht in: | Bioconjugate chemistry 2010-11, Vol.21 (11), p.1956 |
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| container_issue | 11 |
| container_start_page | 1956 |
| container_title | Bioconjugate chemistry |
| container_volume | 21 |
| creator | Pozzo, Alma Dal Esposito, Emiliano Ni, Minghong Muzi, Laura Pisano, Claudio Bucci, Federica Vesci, Loredana Castorina, Massimo Penco, Sergio |
| description | Eight conjugates of a novel camptothecin derivative (Namitecan, NMT) with RGD peptides have been synthesized and biologically evaluated. This study focused on factors that optimize the drug linkage to the transport vector. The different linkages investigated consist of heterofunctional glycol fragments and a lysosomally cleavable peptide. The linkage length and conformation were systematically modified with the purpose to understand their effect on receptor affinity, systemic stability, cytotoxicity, and solubility of the corresponding conjugates. Among the new conjugates prepared, C6 and C7 showed high receptor affinity and tumor cell adhesion, acceptable stability in murine blood, and high cytotoxic activity (IC50 = 8 nM). The rationale, synthetic strategy, and preliminary biological results will be presented. [PUBLICATION ABSTRACT] |
| format | Article |
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| fulltext | fulltext |
| identifier | ISSN: 1043-1802 |
| ispartof | Bioconjugate chemistry, 2010-11, Vol.21 (11), p.1956 |
| issn | 1043-1802 1520-4812 |
| language | eng |
| recordid | cdi_proquest_journals_815165244 |
| source | ACS Publications |
| subjects | Cell adhesion & migration Chemical compounds Chemical synthesis Drug therapy Peptides Proteins Toxicity Tumors |
| title | Conjugates of a Novel 7-Substituted Camptothecin with RGD-Peptides as [alpha]^sub v^[Beta]^sub 3^ Integrin Ligands: An Approach to Tumor-Targeted Therapy |
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