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 journalArticlepeer-review

11 Scopus citations


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
Issue number10
StatePublished - Oct 21 2015

ASJC Scopus subject areas

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


Dive into the research topics of 'Conjugation Approach to Produce a Staphylococcus aureus Synbody with Activity in Serum'. Together they form a unique fingerprint.

Cite this