Anticancer activity of drug conjugates in head and neck cancer cells.
Sexually transmitted oral cancer/head and neck cancer is increasing rapidly. Human papilloma virus (HPV) is playing a role in the pathogenesis of a subset of squamous cell carcinoma of head and neck (SCCHN). Paclitaxel is a widely used anticancer drug for breast, ovarian, testicular, cervical, non-small cell lung, head and neck cancer. However, it is water insoluble and orally inactive. We report the synthesis of water soluble nanosize conjugates of paclitaxel, branched PEG, and EGFR-targeting peptide by employing native chemical ligation. We performed a native chemical ligation between the N-hydroxy succinimide (NHS) ester of paclitaxel succinate and cysteine at pH 6.5 to give the cysteine-conjugated paclitaxel derivative. The thiol functionality of cysteine was activated and subsequently conjugated to multiarm thiol-PEG to obtain the paclitaxel branched PEG conjugate. Finally, we conjugated an EGFR-targeting peptide to obtain conjugates of paclitaxel, branched PEG, and EGFR-targeting peptide. These conjugates show anticancer activity against squamous cell carcinoma of head and neck cells (SCCHN, Tu212).
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Emory University, 1365 C Clifton Road, Atlanta, GA 30322 and Glycosyn LLC, Medford, MA 02155.
Debatosh
D
Majumdar
Glycosyn LLC, Medford, MA 02155.
Mohammad Aminur
MA
Rahman
Glycosyn LLC, Medford, MA 02155.
Zhuo Georgia
ZG
Chen
Glycosyn LLC, Medford, MA 02155, dmshin@emory.edu.
Dong M
DM
Shin
D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000821:virology; D045744:Cell Line, Tumor; D003545:Cysteine / Q000737:chemistry; D004952:Esters / Q000737:chemistry; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019906:Nuclear Magnetic Resonance, Biomolecular; D017239:Paclitaxel / Q000737:chemistry / Q000627:therapeutic use*; D030361:Papillomavirus Infections / Q000150:complications; D012749:Sexually Transmitted Diseases
D000970:Antineoplastic Agents; D004952:Esters; D003545:Cysteine; D017239:Paclitaxel