Combinational chemotherapy is a highly effective treatment for cancer, and often necessary in metastatic phase of the diseases. Use of a carrier system is often necessary for efficient delivery of multiple drugs to control their ratio during drug administration. Here, the conjugation of drugs to hybrid peptides as a carrier is used to administer this combinational therapy. The drugs chosen for this study as a model system are used in the aggressive and metastatic breast cancers: Paclitaxel, Doxorubicin, and 5-Fluorouracil. Each drug is conjugated to a hybrid peptide by first being modified with a succinic linker. HNMR showed that the modification of Doxorubicin, Paclitaxel, and 5-Fluorouracil with succinic linker was successful. Upon conformation of the addition of the succinic linker to each drug, the modified drugs were conjugated to hybrid peptides via the peptide coupling agent HATU (O-(7- azabenzotriazol-1-yl)-N, N, N`,N`-tetramethyluronium hexafluorophosphate). DOX and 5FU were conjugated to hybrid peptide, which contains a homotrimer CMP domain. PTX was conjugated HT1 peptide, which contains a heterotrimer CMP domain. The conjugation of the PTX to HT1 is a first step in synthesis of heterotrimer hybrid peptide capable of combination therapy that consists of three drugs. The conjugations were confirmed with NMR, ESI-MS and HPLC studies. The formation of the heterotrimer peptide HT123 was confirmed with Circular Dichroism Spectroscopy. The DOX and 5FU were conjugated to HT2 and HT3 peptides to complete the helix in the heterotrimer to form of the nanocarrier. Upon conjugation of all drugs to hybrid peptides with heterotrimer CMP domains cell viability study can be used to confirm the efficiency of this combinational therapy and potential synergistic effects due to a single carrier.
|Commitee:||Schwans, Jason, McAbee, Douglas|
|School:||California State University, Long Beach|
|Department:||Chemistry and Biochemistry|
|School Location:||United States -- California|
|Source:||MAI 81/1(E), Masters Abstracts International|
|Keywords:||Breast cancer, Cell penetrating peptides, Collagen mimetic peptides, Combinational chemotherapy, Drug delivery, Hybrid peptide|
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