title: A novel delivery platform for therapeutic peptides.
abstract: Although many peptides have therapeutic effects against diverse disease, their short half-lives in vivo hurdle their application as drug candidates. To extend the short elimination half-lives of therapeutic peptides, we developed a novel delivery platform for therapeutic peptides using an anti-hapten antibody and its corresponding hapten. We selected cotinine because it is non-toxic, has a well-studied metabolism, and is physiologically absent. We conjugated WKYMVm-NH2, an anti-sepsis therapeutic peptide, to cotinine and showed that the conjugated peptide in complex with an anti-cotinine antibody has a significantly improved in vivo half-life while retaining its therapeutic efficacy. We suggest that this novel delivery platform for therapeutic peptides will be very useful to develop effective peptide therapeutics.
authors.affiliation: Department of Biochemistry and Molecular Biology, Seoul National University School of Medicine, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University, Seoul, Republic of Korea.
authors.forename: Sunyoung
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University, Suwon, Republic of Korea.
authors.forename: Sang Doo
authors.initials: SD
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University, Suwon, Republic of Korea; Mitochondria Hub Regulation Center, Dong-A University, Busan, Republic of Korea.
authors.forename: Ha Young
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Molecular Biology, Seoul National University School of Medicine, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University, Seoul, Republic of Korea.
authors.forename: Dobeen
authors.initials: D
authors.lastname: Hwang
authors.affiliation: Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Joon Seong
authors.initials: JS
authors.lastname: Park
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University, Suwon, Republic of Korea; Mitochondria Hub Regulation Center, Dong-A University, Busan, Republic of Korea; Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea. Electronic address: yoesik@skku.edu.
authors.forename: Yoe-Sik
authors.initials: YS
authors.lastname: Bae
authors.affiliation: Department of Biochemistry and Molecular Biology, Seoul National University School of Medicine, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University, Seoul, Republic of Korea. Electronic address: jjhchung@snu.ac.kr.
authors.forename: Junho
authors.initials: J
authors.lastname: Chung
mesh_terms: D000818:Animals; D002460:Cell Line; D003367:Cotinine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D051379:Mice; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D009842:Oligopeptides / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D011485:Protein Binding; D018805:Sepsis / Q000175:diagnosis* / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D009842:Oligopeptides; C113617:Trp-Lys-Tyr-Met-Val-Met; D003367:Cotinine
keywords: Delivery; Peptide; Sepsis; Stability; Therapeutics