Synthesis and activity of folate conjugated didemnin B for potential treatment of inflammatory diseases

Bioorganic & Medicinal Chemistry Letters
2012.0

Abstract

A folate receptor targeted didemnin B conjugate was synthesized using a hydrophilic peptide spacer linked to folate via a releasable disulfide carbonate linker. Cell cytotoxicity and TNF-α inhibition in RAW264.7 macrophage-like cells exhibited IC(50)s of 13 and 5 nM, respectively. Folate didemnin B was found to be ∼50-100 fold more potent than didemnin B itself. More importantly, activity of the prodrug was blocked by excess folic acid, demonstrating receptor-mediated cellular uptake of the conjugate.

Knowledge Graph

Similar Paper

Synthesis and activity of folate conjugated didemnin B for potential treatment of inflammatory diseases
Bioorganic & Medicinal Chemistry Letters 2012.0
Preparation and in Vitro Photodynamic Activities of Folate-Conjugated Distyryl Boron Dipyrromethene Based Photosensitizers
Journal of Medicinal Chemistry 2013.0
Design, synthesis and biological evaluation of a highly-potent and cancer cell selective folate–taxoid conjugate
Bioorganic & Medicinal Chemistry 2015.0
Folic acid conjugates of a bleomycin mimic for selective targeting of folate receptor positive cancer cells
Bioorganic & Medicinal Chemistry Letters 2019.0
Inhibition of Protein Synthesis by Didemnins:  Cell Potency and SAR
Journal of Medicinal Chemistry 2000.0
Antineoplastic activity of didemnin congeners: nordidemnin and modified chain analogs
Journal of Medicinal Chemistry 1991.0
Folic Acid–Peptide Conjugates Combine Selective Cancer Cell Internalization with Thymidylate Synthase Dimer Interface Targeting
Journal of Medicinal Chemistry 2021.0
Light induced drug release from a folic acid-drug conjugate
Bioorganic & Medicinal Chemistry Letters 2017.0
Synthesis and anti-cancer evaluation of folic acid-peptide- paclitaxel conjugates for addressing drug resistance
European Journal of Medicinal Chemistry 2019.0
Synthesis and Antitumor Activity of a Novel Series of 6-Substituted Pyrrolo[2,3-d]pyrimidine Thienoyl Antifolate Inhibitors of Purine Biosynthesis with Selectivity for High Affinity Folate Receptors and the Proton-Coupled Folate Transporter over the Reduced Folate Carrier for Cellular Entry
Journal of Medicinal Chemistry 2010.0