Enhancement of binding affinity of folate to its receptor by peptide conjugation

Roopa Dharmatti, Hideyuki Miyatake*, Avanashiappan Nandakumar, Motoki Ueda, Kenya Kobayashi, Daisuke Kiga, Masayuki Yamamura, Yoshihiro Ito

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


(1) Background: The folate receptor (FR) is a target for cancer treatment and detection. Expression of the FR is restricted in normal cells but overexpressed in many types of tumors. Folate was conjugated with peptides for enhancing binding affinity to the FR. (2) Materials and Methods: For conjugation, folate was coupled with propargyl or dibenzocyclooctyne, and 4-azidophenylalanine was introduced in peptides for “click” reactions. We measured binding kinetics including the rate constants of association (ka) and dissociation (kd) of folate-peptide conjugates with purified FR by biolayer interferometry. After optimization of the conditions for the click reaction, we successfully conjugated folate with designed peptides. (3) Results: The binding affinity, indicated by the equilibrium dissociation constant (KD), of folate toward the FR was enhanced by peptide conjugation. The enhanced FR binding affinity by peptide conjugation is a result of an increase in the number of interaction sites. (4) Conclusion: Such peptide-ligand conjugates will be important in the design of ligands with higher affinity. These high affinity ligands can be useful for targeted drug delivery system.

Original languageEnglish
Article number2152
JournalInternational journal of molecular sciences
Issue number9
Publication statusPublished - 2019 May 1


  • Biolayer interferometry
  • Click reaction
  • Folate
  • Folate receptor
  • Peptide conjugation

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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