PUBLICATION
Acid-Activated Melittin for Targeted and Safe Antitumor Therapy
- Authors
- Luo, L., Wu, W., Sun, D., Dai, H.B., Wang, Y., Zhong, Y., Wang, J.X., Maruf, A., Nurhidayah, D., Zhang, X.J., Wang, Y., Wang, G.X.
- ID
- ZDB-PUB-190706-16
- Date
- 2018
- Source
- Bioconjugate Chemistry 29: 2936-2944 (Journal)
- Registered Authors
- Wang, Guixue, Wang, Yi, Zhang, Xiaojuan
- Keywords
- none
- MeSH Terms
-
- Acids/chemistry*
- Animals
- Antineoplastic Agents/chemistry*
- Antineoplastic Agents/pharmacology
- Antineoplastic Agents/therapeutic use*
- Biocompatible Materials
- Cell Survival/drug effects
- Chromatography, High Pressure Liquid
- Drug Delivery Systems*
- HeLa Cells
- Hemolysis/drug effects
- Humans
- Hydrogen-Ion Concentration
- Larva/drug effects
- Maleic Anhydrides/chemistry
- Melitten/chemistry*
- Melitten/pharmacology
- Melitten/therapeutic use*
- Neoplasms/drug therapy*
- Proton Magnetic Resonance Spectroscopy
- Reproducibility of Results
- Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
- Zebrafish/growth & development
- PubMed
- 30148623 Full text @ Bioconjug. Chem.
Citation
Luo, L., Wu, W., Sun, D., Dai, H.B., Wang, Y., Zhong, Y., Wang, J.X., Maruf, A., Nurhidayah, D., Zhang, X.J., Wang, Y., Wang, G.X. (2018) Acid-Activated Melittin for Targeted and Safe Antitumor Therapy. Bioconjugate Chemistry. 29:2936-2944.
Abstract
Melittin (MLT), as a natural active biomolecule, can penetrate the tumor cell membrane to play a role in cancer treatment and will attract more attention in future development of antitumor drugs. The main component of natural bee venom MLT was modified by introducing a pH-sensitive amide bond between the 2,3-dimethyl maleimide (DMMA) and the lysine (Lys) of MLT (MLT-DMMA). MLT and its corresponding modified peptide MLT-DMMA were used for antitumor and biocompatibility validation. The biomaterial characteristics were tested by MALDI-TOF MS, 1H NMR, IUPAC and HPLC, cell viability, hemolytic and animal experiment safety evaluation. Compared with the primary melittin, the modified peptide showed decreased surface charge and low cytotoxicity in physiological conditions. Moreover, cell assays confirmed the acid-activated conversion of amide bond resulting in adequate safety during delivery and timely antitumor activity in tumor lesions. Thus, MLT-DMMA provided a feasible platform to improve the targeted and safe antitumor applications.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping