Conjugation Approach To Produce a Staphylococcus aureus Synbody with Activity in Serum
| Autor: | Stephen Albert Johnston, Chris W. Diehnelt, Mariana Ferrer Fuenmayor, John C. Lainson |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Methicillin-Resistant Staphylococcus aureus
medicine.drug_class Molecular Sequence Data Antibiotics Biomedical Engineering Succinimides Pharmaceutical Science Bioengineering Microbial Sensitivity Tests medicine.disease_cause Maleimides Hydrolysis chemistry.chemical_compound medicine Animals Amino Acid Sequence Sulfhydryl Compounds Peptide sequence Maleimide Pharmacology Mice Inbred BALB C Chemistry Organic Chemistry Albumin Blood proteins Anti-Bacterial Agents Biochemistry Staphylococcus aureus Female Peptides Biotechnology Conjugate |
| Zdroj: | Bioconjugate Chemistry. 26:2125-2132 |
| ISSN: | 1520-4812 1043-1802 |
| DOI: | 10.1021/acs.bioconjchem.5b00420 |
| Popis: | Synbodies show promise as a new class of synthetic antibiotics. Here, we explore improvements in their activity and production through conjugation chemistry. Maleimide conjugation is a widely used conjugation strategy due to its high yield, selectivity, and low cost. We used this strategy to conjugate two antibacterial peptides to produce a bivalent antibacterial peptide, called a synbody that has bactericidal activity against methicillin resistant Staphylococcus aureus (MRSA). The synbody was prepared by conjugation of a partially d-amino acid substituted synthetic antibacterial peptide to a bis-maleimide scaffold. The synbody slowly degrades in serum, but also undergoes exchange reactions with other serum proteins, such as albumin. Therefore, we hydrolyzed the thiosuccinimide ring using a mild hydrolysis protocol to produce a new synbody with similar bactericidal activity. The synbody was now resistant to exchange reactions and maintained bactericidal activity in serum for 2 h. This work demonstrates that low-cost maleimide coupling can be used to produce antibacterial peptide conjugates with activity in serum. |
| Databáze: | OpenAIRE |
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