The effect of acidic pH on the inhibitory efficacy of peptides against the interaction ICAM-1/LFA-1 studied by surface plasmon resonance (SPR).
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.
Institute of Biophotonics, National Yang-Ming University, No. 155, Section 2, Linong Street, Taipei 11221, Taiwan, ROC; Research Center for Applied Sciences, Academia Sinica, Taipei 11529, Taiwan, ROC.
Shu-Han
SH
Wu
Immune Effector Cells Group, Aragón Health Research Institute (IIS Aragón), Biomedical Research Centre of Aragón (CIBA), Zaragoza 50009, Spain; Instituto de Carboquímica ICB-CSIC, Zaragoza 50018, Spain; Department of Biochemistry and Molecular and Cell Biology, Fac. Ciencias, University of Zaragoza, Zaragoza 50009, Spain.
David
D
Núnez
Institute of Biophotonics, National Yang-Ming University, No. 155, Section 2, Linong Street, Taipei 11221, Taiwan, ROC.
Shih-Yang
SY
Hu
Immune Effector Cells Group, Aragón Health Research Institute (IIS Aragón), Biomedical Research Centre of Aragón (CIBA), Zaragoza 50009, Spain; Instituto de Carboquímica ICB-CSIC, Zaragoza 50018, Spain.
María Pilar
MP
Domingo
Institute of Imaging and Biomedical Photonics, National Chiao Tung University, Tainan 71150, Taiwan, ROC.
Yi-Chun
YC
Chen
Institute of Biophotonics, National Yang-Ming University, No. 155, Section 2, Linong Street, Taipei 11221, Taiwan, ROC; Research Center for Applied Sciences, Academia Sinica, Taipei 11529, Taiwan, ROC.
Pei-Kuen
PK
Wei
Immune Effector Cells Group, Aragón Health Research Institute (IIS Aragón), Biomedical Research Centre of Aragón (CIBA), Zaragoza 50009, Spain; Department of Biochemistry and Molecular and Cell Biology, Fac. Ciencias, University of Zaragoza, Zaragoza 50009, Spain; Aragón I+D Foundation (ARAID), Government of Aragon, Zaragoza 50004, Spain; Nanoscience Institute of Aragon (INA), Aragón I+D Foundation (ARAID), University of Zaragoza, Zaragoza 50009, Spain. Electronic address: pardojim@unizar.es.
Julián
J
Pardo
Immune Effector Cells Group, Aragón Health Research Institute (IIS Aragón), Biomedical Research Centre of Aragón (CIBA), Zaragoza 50009, Spain; Instituto de Carboquímica ICB-CSIC, Zaragoza 50018, Spain. Electronic address: eva@icb.csic.es.
Eva M
EM
Gálvez
Institute of Biophotonics, National Yang-Ming University, No. 155, Section 2, Linong Street, Taipei 11221, Taiwan, ROC; Biophotonics & Molecular Imaging Research Center (BMIRC), National Yang-Ming University, No. 155, Section 2, Linong Street, Taipei 11221, Taiwan, ROC. Electronic address: aechiou@ym.edu.tw.
Arthur
A
Chiou
D002460:Cell Line; D006801:Humans; D006863:Hydrogen-Ion Concentration; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000737:chemistry / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D025941:Protein Interaction Mapping / Q000379:methods; D060066:Protein Interaction Maps / Q000187:drug effects; D011994:Recombinant Proteins / Q000378:metabolism; D020349:Surface Plasmon Resonance / Q000379:methods*
D016169:Lymphocyte Function-Associated Antigen-1; D010455:Peptides; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D008274:Magnesium
Acid pH; ICAM-1; LFA-1; Peptide drug; Surface plasmon resonance (SPR)