A Versatile Approach to Noncanonical, Dynamic Covalent Single- and Multi-Loop Peptide Macrocycles for Enhancing Antimicrobial Activity
| Autor: | Valarie Del Rio, Tiffany A. Lu, P Rogelio Escamilla, James F. Reuther, Eric V. Anslyn, Bryan William Davies, Andrew C. Goodrich |
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| Rok vydání: | 2018 |
| Předmět: |
Macrocyclic Compounds
Biocompatibility Sequence (biology) Peptide Chemistry Techniques Synthetic 010402 general chemistry Hydrazide 01 natural sciences Biochemistry Oligomer Catalysis Article chemistry.chemical_compound Colloid and Surface Chemistry Peptide synthesis Humans Amino Acid Sequence Peptide sequence chemistry.chemical_classification Bacteria 010405 organic chemistry Proteins General Chemistry Bacterial Infections Combinatorial chemistry 0104 chemical sciences Anti-Bacterial Agents chemistry Covalent bond Peptides |
| Zdroj: | Journal of the American Chemical Society. 140(10) |
| ISSN: | 1520-5126 |
| Popis: | Peptide oligomers offer versatile scaffolds for the formation of potent antimicrobial agents due to their high sequence versatility, inherent biocompatibility, and chemical tunability. Though many methods exist for the formation of peptide-based macrocycles (MCs), increasingly pervasive in commercial antimicrobial therapeutics, the introduction of multiple looped structures into a single peptide oligomer remains a significant challenge. Herein, we report the utilization of dynamic hydrazone condensation for the versatile formation of single-, double-, and triple-loop peptide MCs using simple dialdehyde or dihydrazide small-molecule cross-linkers, as confirmed by MALDI-TOF MS, HPLC, and SDS-PAGE. Furthermore, incorporation of aldehyde-containing side chains onto peptides synthesized from hydrazide C-terminal resins resulted in tunable peptide MC assemblies formed directly upon resin cleavage post solid-phase peptide synthesis. Both of these types of dynamic covalent assemblies produced significant enhancements to overall antimicrobial properties when introduced into a known antimicrobial peptide, buforin II, when compared to the original unassembled sequence. |
| Databáze: | OpenAIRE |
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