Functionalization of peptide nucleolipid bioconjugates and their structure anti-cancer activity relationship studies
| Autor: | Christopher N. Cultrara, Mariana Phillips, Niki Rana, David Sabatino |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cell Survival Clinical Biochemistry Pharmaceutical Science Antineoplastic Agents Apoptosis Peptide 01 natural sciences Biochemistry Reductive amination Structure-Activity Relationship Surface-Active Agents 03 medical and health sciences Drug Discovery Amphiphile Tumor Cells Cultured Humans Molecular Biology Peptide sequence Cell Proliferation chemistry.chemical_classification Bioconjugation Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Organic Chemistry Biological activity Lipids 0104 chemical sciences 030104 developmental biology chemistry Cancer cell Molecular Medicine Drug Screening Assays Antitumor Peptides Conjugate |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 27:4019-4023 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2017.07.056 |
| Popis: | In the search for more potent peptide-based anti-cancer conjugates the generation of new, functionally diverse nucleolipid derived D-(KLAKLAK)2-AK sequences has enabled a structure and anti-cancer activity relationship study. A reductive amination approach was key for the synthesis of alkylamine, diamine and polyamine derived nucleolipids as well as those incorporating heterocyclic functionality. The carboxy-derived nucleolipids were then coupled to the C-terminus of the D-(KLAKLAK)2-AK killer peptide sequence and produced with and without the FITC fluorophore for investigating biological activity in cancer cells. The amphiphilic, α-helical peptide-nucleolipid bioconjugates were found to exhibit variable effects on the viability of MM.1S cells, with the histamine derived nucleolipid peptide bioconjugate displaying the most significant anti-cancer effects. Thus, functionally diverse nucleolipids have been developed to fine-tune the structure and anti-cancer properties of killer peptide sequences, such as D-(KLAKLAK)2-AK. |
| Databáze: | OpenAIRE |
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