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Peptide Synthesis> | CXCL12 was chemically synthesized as previously.54 Histidine tagged HMGB1 was produced at the Institute of Research in Biomedicine Protein Facility (Bellinzona, Switzerland) as previously described,12 and stored in phosphate-buffered saline (PBS; D8537, Sigma Aldrich, Saint Louis, MO, USA). All the peptides were custom-synthesized and HPLC-purified by GenScript (New Jersey, USA). Peptides were reconstituted with DMSO and stored at −20 ºC. HPLC-MS was used to confirm 98% or higher purity for each peptide. | Get A Quote |
During inflammatory reactions, the production and release of chemotactic factors guide the recruitment of selective leukocyte subpopulations. HMGB1 and the chemokine CXCL12, both released in the microenvironment, form a heterocomplex, which exclusively acts on the chemokine receptor CXCR4, enhancing cell migration and, in some pathological conditions such as Rheumatoid Arthritis, exacerbating the immune response. An excessive cell influx at the inflammatory site can be diminished by disrupting the heterocomplex. Here, we report the computationally driven identification of a novel peptide (HBP08), which binds HMGB1 with the highest affinity reported so far (Kd of 0.8 ± 0.1 μM), able to selectively inhibit the... More