A novel family of hybrid peptides consisting of cell penetrating peptides and collagen mimetic peptides was developed to be a promising drug carrier for paclitaxel. Conjugation of paclitaxel to lysine groups in hybrid peptides was successfully accomplished using HATU-mediated coupling with 17% yield and confirmed with HPLC, NMR, MALDI-TOF characterizations. Conformational changes of several hybrid peptides were examined using Circular Dichroism Spectroscopy. Their transition temperatures of unfolding (helix-to-coil transition) were determined ranging from 15.3 to 63.7 °C. We confirmed that the overall propensity of folding is highly dependent on the peptide sequence and number of amino acids in the sequence. The cytotoxicity of the paclitaxel conjugate was tested using cell proliferation assays. The IC50 of the paclitaxel conjugate (27.5 nM) was slightly higher than pure paclitaxel (15.8 nM), which indicates that the hybrid peptides are a promising class of drug carrier that enables the delivery of paclitaxel across the cellular membrane.
|Commitee:||Schwans, Jason, Weers, Paul|
|School:||California State University, Long Beach|
|Department:||Chemistry and Biochemistry|
|School Location:||United States -- California|
|Source:||MAI 55/02M(E), Masters Abstracts International|
|Keywords:||Cell-penetrating peptides, Collagen peptides, Conjugation, Drug delivery, Paclitaxel, Triple helix|
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