The effect of acidic pH on the inhibitory efficacy of peptides against the interaction ICAM-1/LFA-1 studied by surface plasmon resonance (SPR)

Shu Han Wu, David Núnez, Shih Yang Hu, María Pilar Domingo, Yi-Chun Chen, Pei Kuen Wei, Julián Pardo, Eva M. Gálvez, Arthur Chiou*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Synthetic peptides have been developed for therapeutic applications for decades. The therapeutic efficacy often depends not only on the stabilization of the peptides but also on their binding specificity and affinity to the target molecules to interfere with designated molecular interaction. In this study, the binding affinity of human intercellular adhesion molecule 1 (ICAM-1) chimera and leukocyte function-associated antigen-1 (LFA-1) derived peptides was measured by surface plasmon resonance (SPR) detection, and the results were compared with that of the interaction (of ICAM-1) with the LFA-1 whole protein. To mimic diverse pathological situations in vivo where a low pH has been reported, we studied pH regulated binding affinity of ICAM-1/LFA-1 at pH 7.4, 6.5, and 4.0 without and with magnesium ion. We have found that the binding affinity of LFA-1 whole protein and ICAM-1 increases significantly as the environmental pH decreases, regardless of the absence or the presence of magnesium ion. The affinity of different (LFA-1) derived peptides also depends on the pH, although in all cases the peptides retain its ability to inhibit ICAM-1/LFA-1 interaction. The biomedical relevance of these data has been confirmed using a cell aggregation assay, suggesting that LFA-1 derived peptides show great potential for peptide drug development with a wide functional window of pH range for potential applications in LFA-1 related tumor therapy and autoimmune disease treatment.

Original languageEnglish
Pages (from-to)159-166
Number of pages8
JournalBiosensors and Bioelectronics
Volume56
DOIs
StatePublished - 15 Jun 2014

Keywords

  • Acid pH
  • ICAM-1
  • LFA-1
  • Peptide drug
  • Surface plasmon resonance (SPR)

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