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Poly(amidoamine) Dendrimer–Methotrexate Conjugates: The Mechanism of Interaction with Folate Binding Protein
[Image: see text] Generation 5 poly(amidoamine) (G5 PAMAM) methotrexate (MTX) conjugates employing two small molecular linkers, G5-(COG-MTX)(n), G5-(MFCO-MTX)(n) were prepared along with the conjugates of the G5-G5 (D) dimer, D-(COG-MTX)(n), D-(MFCO-MTX)(n). The monomer G5-(COG-MTX)(n) conjugates ex...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical
Society
2014
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224518/ https://www.ncbi.nlm.nih.gov/pubmed/25222480 http://dx.doi.org/10.1021/mp500608s |
Sumario: | [Image: see text] Generation 5 poly(amidoamine) (G5 PAMAM) methotrexate (MTX) conjugates employing two small molecular linkers, G5-(COG-MTX)(n), G5-(MFCO-MTX)(n) were prepared along with the conjugates of the G5-G5 (D) dimer, D-(COG-MTX)(n), D-(MFCO-MTX)(n). The monomer G5-(COG-MTX)(n) conjugates exhibited only a weak, rapidly reversible binding to folate binding protein (FBP) consistent with monovalent MTX binding. The D-(COG-MTX)(n) conjugates exhibited a slow onset, tight-binding mechanism in which the MTX first binds to the FBP, inducing protein structural rearrangement, followed by polymer–protein van der Waals interactions leading to tight-binding. The extent of irreversible binding is dependent on total MTX concentration and no evidence of multivalent MTX binding was observed. |
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