title: From Erythropoietin to Its Peptide Derivatives: Smaller but Stronger.
abstract: 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.
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China and Shanghai Key Laboratory of Organ Transplantation, Shanghai, 200032. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China and Shanghai Key Laboratory of Organ Transplantation, Shanghai, 200032. China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University; Shanghai Key Laboratory of Organ Transplantation; 180 Fenglin Road, Shanghai, 200032. China.
authors.forename: Tongyu
authors.initials: T
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D003500:Cyclization; D053648:Cytokine Receptor Common beta Subunit / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006207:Half-Life; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000493:pharmacokinetics / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D020011:Protective Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D017467:Receptors, Erythropoietin / Q000235:genetics / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D053648:Cytokine Receptor Common beta Subunit; C554270:EPO protein, human; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D020011:Protective Agents; D017467:Receptors, Erythropoietin; C585201:glutaminyl-glutamyl-glutaminyl-leucyl-glutamyl-arginyl-alanyl-leucyl-asparagyl-seryl-serine; D004921:Erythropoietin
keywords: CHBP; Erythropoietin; HBSP; derivatives; ischemia-reperfusion injury; tissue protection