Erythropoietin (EPO), recognized early as a tissue protective agent, can trigger antiinflammatory
and anti-apoptotic processes to delimit injury and promote repair by binding tissueprotective
receptor (TPR). However, only at a high dosage can EPO exert tissue protective effect,
which may elicit severe side-effects at the meantime. Helix B surface peptide (HBSP), a 11-amnio acid
sequence derived from the non-erythropoietic helix B of EPO, not only shows higher affinity to TPR
but also plays a more specific and powerful role in tissue protection without erythropoietic side-effects.
While it has obvious merits, the 2-min plasma half-life of HBSP restricts its application in vivo. Therefore,
based on the amino acid sequence of HBSP, we originally designed and synthesized thioethercyclized
helix B peptide (CHBP) for an increased resistance to proteolytic degradation as well as an
improved tissue protective potency, implying a brighter prospective for translational application. In this
review, we will mainly discuss the development from EPO to CHBP, the merits and limitation of
CHBP and the probable mechanism mediating tissue protection.