title: A novel analog of antimicrobial peptide Polybia-MPI, with thioamide bond substitution, exhibits increased therapeutic efficacy against cancer and diminished toxicity in mice.
abstract: Polybia-MPI (MPI), a short cationic α-helical antimicrobial peptide, exhibited excellent anticancer activity and selectivity in vitro in our previous studies. To improve its in vivo application, we synthesized an analog (MPI-1) of MPI by replacing the C terminal amide -[CO-NH(2)] with thioamide -ψ[CS-NH(2)]. Although there is just one atom difference, the MPI-1 exhibited some surprising properties. In vitro studies revealed that MPI-1 exhibited relatively high lytic activity over MPI, whereas its stability to enzymatic degradation in serum was improved remarkably. Despite the enhanced toxicity in vitro, MPI-1 exhibited significantly lower mortality to mice than MPI at 75 mg/kg. Importantly, in vivo anticancer activity study indicated that MPI-1 could remarkably suppress the growth of sarcoma xenograft tumors more efficiently than MPI. Therefore, the significantly improved anticancer activity and predominantly lower in vivo toxicity might allow MPI-1 to be a good candidate for future anticancer treatment.
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Lanzhou University, 222 Tian Shui South Road, Lanzhou, Gansu 730000, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Li-Wei
authors.initials: LW
authors.lastname: Liu
authors.forename: Kai-Rong
authors.initials: KR
authors.lastname: Wang
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Song
authors.forename: Jie-Xi
authors.initials: JX
authors.lastname: Yan
authors.forename: Zhen-Ya
authors.initials: ZY
authors.lastname: Li
authors.forename: Bang-Zhi
authors.initials: BZ
authors.lastname: Zhang
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use; D002460:Cell Line; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D019476:Insect Proteins / Q000737:chemistry / Q000627:therapeutic use; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy*; D013854:Thioamides / Q000737:chemistry*; D016896:Treatment Outcome; D014862:Wasp Venoms / Q000737:chemistry
chemical_list: D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; D019476:Insect Proteins; D013854:Thioamides; D014862:Wasp Venoms