Syndiotactic peptides for targeted delivery
| Autor: | Gaurav Jerath, Ruchika Goyal, Vibin Ramakrishnan, Vishal Trivedi, Thankayyan R. Santhoshkumar |
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| Rok vydání: | 2019 |
| Předmět: |
0206 medical engineering
Protein design Biomedical Engineering Peptide Cell-Penetrating Peptides 02 engineering and technology Endocytosis Biochemistry Clathrin Biomaterials Transduction (genetics) Animals Humans Molecular Biology chemistry.chemical_classification Drug Carriers biology Chemistry General Medicine 021001 nanoscience & nanotechnology 020601 biomedical engineering In vitro Anti-Bacterial Agents HEK293 Cells Targeted drug delivery Cancer cell biology.protein Cattle 0210 nano-technology HeLa Cells Biotechnology |
| Zdroj: | Acta Biomaterialia. 87:130-139 |
| ISSN: | 1742-7061 |
| Popis: | Lack of cell-type specificity and proteolytic susceptibility have long been the major bottlenecks for the development of peptide-based biomaterials for targeted drug delivery. Though a poly-l backbone provides the adaptability to re-conform the peptide structure to bind to a receptor, it also makes the peptide more susceptible to proteolytic cleavage. We have attempted to address this issue by designing a set of syndiotactic peptides de novo, with alternating l- and d-amino acids in succession. The designed peptides have higher rates of cellular uptake than the Tat (48-60) peptide in breast and cervical cancer cells. The uptake is independent of concentration, temperature and endocytosis (clathrin mediated). Importantly, the peptides are stable in both human plasma and bovine serum. The peptide-drug conjugates are much less toxic to the non-cancerous cells than cancer cells. The designed peptides are a step forward towards the development of targeted drug delivery vectors on peptide templates. STATEMENT OF SIGNIFICANCE: Present options in chemotherapy have multiple side effects arising from the lack of cell-type specificity, which makes them synonymous with "a Pyrrhic victory". Proteolytic susceptibility and non-specificity towards cancer cells has stunted the development of peptide-based biomaterials for targeted drug delivery. We have designed a set of peptides, addressing the above-mentioned roadblocks at an in vitro level. The peptides were designed on the template of a naturally existing peptide antibiotic from Bacillus brevis. The designed peptides have higher rates of cellular transduction than the model peptide (Tat), and is majorly membrane based. The peptides are stable in serum and selective towards cancer cells. Observations presented in this work can potentially take the discipline of de novo design of biomaterial conjugates forward. |
| Databáze: | OpenAIRE |
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