Conjugation Approach to Produce a Staphylococcus aureus Synbody with Activity in Serum

John C. Lainson, Mariana Ferrer Fuenmayor, Stephen Johnston, Chris Diehnelt

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2125-2132
Number of pages8
JournalBioconjugate Chemistry
Volume26
Issue number10
DOIs
StatePublished - Oct 21 2015

Fingerprint

Peptides
Staphylococcus aureus
Serum
Costs and Cost Analysis
Methicillin
Antibiotics
Scaffolds (biology)
Methicillin-Resistant Staphylococcus aureus
Scaffolds
Amino acids
Costs
Blood Proteins
Albumins
Hydrolysis
Anti-Bacterial Agents
Proteins
Amino Acids
maleimide

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Organic Chemistry
  • Pharmaceutical Science
  • Biomedical Engineering
  • Pharmacology

Cite this

Conjugation Approach to Produce a Staphylococcus aureus Synbody with Activity in Serum. / Lainson, John C.; Fuenmayor, Mariana Ferrer; Johnston, Stephen; Diehnelt, Chris.

In: Bioconjugate Chemistry, Vol. 26, No. 10, 21.10.2015, p. 2125-2132.

Research output: Contribution to journalArticle

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