60f39dd5818bb29543685ac36fa76532 intjoumolsci_a2020v21n20p7502.pdf 5a35904fefd2634888eda682963da7f687ff356d intjoumolsci_a2020v21n20p7502.pdf be91c3977785abea4a53c72be43de4fddb749018385ab9f7c0e8acdd2253b2c2 intjoumolsci_a2020v21n20p7502.pdf Title: Chiral Cyclobutane-Containing Cell-Penetrating Peptides as Selective Vectors for Anti-Leishmania Drug Delivery Systems Subject: Two series of new hybrid /-peptides, -CC and -CT, formed by (1S,2R)-3-amino- 2,2,dimethylcyclobutane-1-carboxylic acid joined in alternation to a N-functionalized cis- or trans–amino-l-proline derivative, respectively, have been synthesized and evaluated as cell penetrating peptides (CPP) and as selective vectors for anti-Leishmania drug delivery systems (DDS). They lacked cytotoxicity on the tumoral human cell line HeLa with a moderate cell-uptake on these cells. In contrast, both -CC and -CT tetradecamers were microbicidal on the protozoan parasite Leishmania beyond 25 M, with significant intracellular accumulation. They were conjugated to fluorescent doxorubicin (Dox) as a standard drug showing toxicity beyond 1 M, while free Dox was not toxic. Intracellular accumulation was 2.5 higher than with Dox-TAT conjugate (TAT = transactivator of transcription, taken as a standard CPP). The conformational structure of the conjugates was approached both by circular dichroism spectroscopy and molecular dynamics simulations. Altogether, computational calculations predict that the drug–peptide conjugates adopt conformations that bury the Dox moiety into a cavity of the folded peptide, while the positively charged guanidinium groups face the solvent. The favorable charge/hydrophobicity balance in these CPP improves the solubility of Dox in aqueous media, as well as translocation across cell membranes, making them promising candidates for DDS. Keywords: unnatural -amino acids; foldamers; selective cell-penetrating peptides; anti-Leishmania drug delivery vectors Author: Ona Illa, José-Antonio Olivares, Nerea Gaztelumendi, Laura Martínez-Castro, Jimena Ospina, María-Ángeles Abengozar, Giuseppe Sciortino, Jean-Didier Maréchal, Carme Nogués, Míriam Royo, Luis Rivas and Rosa M. 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2019-04-17) Date: 2022-03-18 02:23:42 CET RepresentationInformation: intjoumolsci_a2020v21n20p7502.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2020-11-16 11:08:16 CET Size: 3618906 Format: PDF Version: 1.5 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 0 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: ぉのぴひはつふっぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸲ Item: Title: げづびふぬぴびぜ〴ぜ〰ちのつぜ〴ぜ〰いどびっふびびどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮ㄩ‾㸊⡜㌷㙜㌷㝜〰いづびどでのぜ〴ぜ〰ちのつぜ〴ぜ〰こべのぴとづびどびぜ〴ぜ〰はてぜ〴ぜ〰ぐづばぴどつづびぜ〴ぜ〰ちのつぜ〴ぜ〰ぃはのなふでちぴづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㈩‾㸊⡜㌷㙜㌷㝜〰ぃべぴはぴはへどっどぴべぜ〴ぜ〰ちのつぜ〴ぜ〰ぃづぬぬふぬちひぜ〴ぜ〰さばぴちにづぜ〴ぜ〰どのぜ〴ぜ〰えづがちぜ〴ぜ〰ぃづぬぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰さばぴちにづ〬ぜ〴ぜ〰きどっひはぢどっどつちぬぜ〴ぜ〰ぁっぴどぶどぴべぜ〴ぜ〰ちのつぜ〴ぜ〰ぉのぴひちっづぬぬふぬちひぜ〴ぜ〰がはっちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ぐづばぴどつづびぜ〴ぜ〰はのぜ〴ぜ〰がづどびとねちのどちぜ〴ぜ〰ぐちひちびどぴづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰ぃいぜ〴ぜ〰こばづっぴひはびっはばべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰きはぬづっふぬちひぜ〴ぜ〰きはつづぬどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Children: Item: Title: いづびどでのぜ〴ぜ〰ちのつぜ〴ぜ〰こべのぴとづびどびぜ〴ぜ〰はてぜ〴ぜ〰ぐづばぴどつづびぜ〴ぜ〰ちのつぜ〴ぜ〰ぃはのなふでちぴづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㈩‾㸊⡜㌷㙜㌷㝜〰ぃべぴはぴはへどっどぴべぜ〴ぜ〰ちのつぜ〴ぜ〰ぃづぬぬふぬちひぜ〴ぜ〰さばぴちにづぜ〴ぜ〰どのぜ〴ぜ〰えづがちぜ〴ぜ〰ぃづぬぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰さばぴちにづ〬ぜ〴ぜ〰きどっひはぢどっどつちぬぜ〴ぜ〰ぁっぴどぶどぴべぜ〴ぜ〰ちのつぜ〴ぜ〰ぉのぴひちっづぬぬふぬちひぜ〴ぜ〰がはっちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ぐづばぴどつづびぜ〴ぜ〰はのぜ〴ぜ〰がづどびとねちのどちぜ〴ぜ〰ぐちひちびどぴづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰ぃいぜ〴ぜ〰こばづっぴひはびっはばべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰きはぬづっふぬちひぜ〴ぜ〰きはつづぬどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: ぃべぴはぴはへどっどぴべぜ〴ぜ〰ちのつぜ〴ぜ〰ぃづぬぬふぬちひぜ〴ぜ〰さばぴちにづぜ〴ぜ〰どのぜ〴ぜ〰えづがちぜ〴ぜ〰ぃづぬぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰さばぴちにづ〬ぜ〴ぜ〰きどっひはぢどっどつちぬぜ〴ぜ〰ぁっぴどぶどぴべぜ〴ぜ〰ちのつぜ〴ぜ〰ぉのぴひちっづぬぬふぬちひぜ〴ぜ〰がはっちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ぐづばぴどつづびぜ〴ぜ〰はのぜ〴ぜ〰がづどびとねちのどちぜ〴ぜ〰ぐちひちびどぴづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰ぃいぜ〴ぜ〰こばづっぴひはびっはばべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰きはぬづっふぬちひぜ〴ぜ〰きはつづぬどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: さばぴちにづ〬ぜ〴ぜ〰きどっひはぢどっどつちぬぜ〴ぜ〰ぁっぴどぶどぴべぜ〴ぜ〰ちのつぜ〴ぜ〰ぉのぴひちっづぬぬふぬちひぜ〴ぜ〰がはっちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ぐづばぴどつづびぜ〴ぜ〰はのぜ〴ぜ〰がづどびとねちのどちぜ〴ぜ〰ぐちひちびどぴづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰ぃいぜ〴ぜ〰こばづっぴひはびっはばべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰きはぬづっふぬちひぜ〴ぜ〰きはつづぬどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: ぃいぜ〴ぜ〰こばづっぴひはびっはばべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰きはぬづっふぬちひぜ〴ぜ〰きはつづぬどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: きはぬづっふぬちひぜ〴ぜ〰きはつづぬどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: きちぴづひどちぬびぜ〴ぜ〰ちのつぜ〴ぜ〰きづぴとはつびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮ㄩ‾㸊⡜㌷㙜㌷㝜〰こべのぴとづびどびぜ〴ぜ〰はてぜ〴ぜ〰ぴとづぜ〴ぜ〰〭ぃぃぜ〴ぜ〰ぐづばぴどつづびぜ〴ぜ〰ぜ〵ぜ〰〴ぜ〲㍜〰〷ぜ〵ㅜ〰〬ぜ〴ぜ〰〭ぃごぜ〴ぜ〰ぐづばぴどつづびぜ〴ぜ〰ぜ〵ぜ〰〸ぜ〲㍜〰〱〱ぜ〵ㅜ〰ぜ〴ぜ〰ちのつぜ〴ぜ〰ごぁご〴〸ぜ〲㍜〰〵〷ぜ〴ぜ〰ぐづばぴどつづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㈩‾㸊⡜㌷㙜㌷㝜〰こべのぴとづびどびぜ〴ぜ〰はてぜ〴ぜ〰ぃべびぴづどのづぜ〴ぜ〰ぅぬはのでちぴづつぜ〴ぜ〰ぐづばぴどつづびぜ〴ぜ〰ぜ〵ぜ〰〱〲ぜ〵ㅜ〰ぜ〴ぜ〰ちのつぜ〴ぜ〰ぜ〵ぜ〰〱〳ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㌩‾㸊⡜㌷㙜㌷㝜〰こべのぴとづびどびぜ〴ぜ〰はてぜ〴ぜ〰いはへはひふぢどっどの〭きぃぃぜ〴ぜ〰ぜ〵ぜ〰〱〴ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㐩‾㸊⡜㌷㙜㌷㝜〰こべのぴとづびどびぜ〴ぜ〰はてぜ〴ぜ〰ぃはのなふでちぴづびぜ〴ぜ〰いはへぜ〲㍜〰ぃぃぜ〴ぜ〰ぜ〵ぜ〰〱〵ぜ〵ㅜ〰ぜ〴ぜ〰ちのつぜ〴ぜ〰いはへぜ〲㍜〰ぃごぜ〴ぜ〰ぜ〵ぜ〰〱〶ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㔩‾㸊⡜㌷㙜㌷㝜〰ぐづばぴどつづぜ〴ぜ〰ちのつぜ〴ぜ〰ぃはのなふでちぴづぜ〴ぜ〰ぐふひどてどっちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㘩‾㸊⡜㌷㙜㌷㝜〰ぐづばぴどつづぜ〴ぜ〰ぃとちひちっぴづひどぺちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱ Children: Item: Title: こべのぴとづびどびぜ〴ぜ〰はてぜ〴ぜ〰ぴとづぜ〴ぜ〰〭ぃぃぜ〴ぜ〰ぐづばぴどつづびぜ〴ぜ〰ぜ〵ぜ〰〴ぜ〲㍜〰〷ぜ〵ㅜ〰〬ぜ〴ぜ〰〭ぃごぜ〴ぜ〰ぐづばぴどつづびぜ〴ぜ〰ぜ〵ぜ〰〸ぜ〲㍜〰〱〱ぜ〵ㅜ〰ぜ〴ぜ〰ちのつぜ〴ぜ〰ごぁご〴〸ぜ〲㍜〰〵〷ぜ〴ぜ〰ぐづばぴどつづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㈩‾㸊⡜㌷㙜㌷㝜〰こべのぴとづびどびぜ〴ぜ〰はてぜ〴ぜ〰ぃべびぴづどのづぜ〴ぜ〰ぅぬはのでちぴづつぜ〴ぜ〰ぐづばぴどつづびぜ〴ぜ〰ぜ〵ぜ〰〱〲ぜ〵ㅜ〰ぜ〴ぜ〰ちのつぜ〴ぜ〰ぜ〵ぜ〰〱〳ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㌩‾㸊⡜㌷㙜㌷㝜〰こべのぴとづびどびぜ〴ぜ〰はてぜ〴ぜ〰いはへはひふぢどっどの〭きぃぃぜ〴ぜ〰ぜ〵ぜ〰〱〴ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㐩‾㸊⡜㌷㙜㌷㝜〰こべのぴとづびどびぜ〴ぜ〰はてぜ〴ぜ〰ぃはのなふでちぴづびぜ〴ぜ〰いはへぜ〲㍜〰ぃぃぜ〴ぜ〰ぜ〵ぜ〰〱〵ぜ〵ㅜ〰ぜ〴ぜ〰ちのつぜ〴ぜ〰いはへぜ〲㍜〰ぃごぜ〴ぜ〰ぜ〵ぜ〰〱〶ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㔩‾㸊⡜㌷㙜㌷㝜〰ぐづばぴどつづぜ〴ぜ〰ちのつぜ〴ぜ〰ぃはのなふでちぴづぜ〴ぜ〰ぐふひどてどっちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㘩‾㸊⡜㌷㙜㌷㝜〰ぐづばぴどつづぜ〴ぜ〰ぃとちひちっぴづひどぺちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱ Item: Title: こべのぴとづびどびぜ〴ぜ〰はてぜ〴ぜ〰ぃべびぴづどのづぜ〴ぜ〰ぅぬはのでちぴづつぜ〴ぜ〰ぐづばぴどつづびぜ〴ぜ〰ぜ〵ぜ〰〱〲ぜ〵ㅜ〰ぜ〴ぜ〰ちのつぜ〴ぜ〰ぜ〵ぜ〰〱〳ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㌩‾㸊⡜㌷㙜㌷㝜〰こべのぴとづびどびぜ〴ぜ〰はてぜ〴ぜ〰いはへはひふぢどっどの〭きぃぃぜ〴ぜ〰ぜ〵ぜ〰〱〴ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㐩‾㸊⡜㌷㙜㌷㝜〰こべのぴとづびどびぜ〴ぜ〰はてぜ〴ぜ〰ぃはのなふでちぴづびぜ〴ぜ〰いはへぜ〲㍜〰ぃぃぜ〴ぜ〰ぜ〵ぜ〰〱〵ぜ〵ㅜ〰ぜ〴ぜ〰ちのつぜ〴ぜ〰いはへぜ〲㍜〰ぃごぜ〴ぜ〰ぜ〵ぜ〰〱〶ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㔩‾㸊⡜㌷㙜㌷㝜〰ぐづばぴどつづぜ〴ぜ〰ちのつぜ〴ぜ〰ぃはのなふでちぴづぜ〴ぜ〰ぐふひどてどっちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㘩‾㸊⡜㌷㙜㌷㝜〰ぐづばぴどつづぜ〴ぜ〰ぃとちひちっぴづひどぺちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱ Item: Title: こべのぴとづびどびぜ〴ぜ〰はてぜ〴ぜ〰いはへはひふぢどっどの〭きぃぃぜ〴ぜ〰ぜ〵ぜ〰〱〴ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㐩‾㸊⡜㌷㙜㌷㝜〰こべのぴとづびどびぜ〴ぜ〰はてぜ〴ぜ〰ぃはのなふでちぴづびぜ〴ぜ〰いはへぜ〲㍜〰ぃぃぜ〴ぜ〰ぜ〵ぜ〰〱〵ぜ〵ㅜ〰ぜ〴ぜ〰ちのつぜ〴ぜ〰いはへぜ〲㍜〰ぃごぜ〴ぜ〰ぜ〵ぜ〰〱〶ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㔩‾㸊⡜㌷㙜㌷㝜〰ぐづばぴどつづぜ〴ぜ〰ちのつぜ〴ぜ〰ぃはのなふでちぴづぜ〴ぜ〰ぐふひどてどっちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㘩‾㸊⡜㌷㙜㌷㝜〰ぐづばぴどつづぜ〴ぜ〰ぃとちひちっぴづひどぺちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱ Item: Title: こべのぴとづびどびぜ〴ぜ〰はてぜ〴ぜ〰ぃはのなふでちぴづびぜ〴ぜ〰いはへぜ〲㍜〰ぃぃぜ〴ぜ〰ぜ〵ぜ〰〱〵ぜ〵ㅜ〰ぜ〴ぜ〰ちのつぜ〴ぜ〰いはへぜ〲㍜〰ぃごぜ〴ぜ〰ぜ〵ぜ〰〱〶ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㔩‾㸊⡜㌷㙜㌷㝜〰ぐづばぴどつづぜ〴ぜ〰ちのつぜ〴ぜ〰ぃはのなふでちぴづぜ〴ぜ〰ぐふひどてどっちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㘩‾㸊⡜㌷㙜㌷㝜〰ぐづばぴどつづぜ〴ぜ〰ぃとちひちっぴづひどぺちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱ Item: Title: ぐづばぴどつづぜ〴ぜ〰ちのつぜ〴ぜ〰ぃはのなふでちぴづぜ〴ぜ〰ぐふひどてどっちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㘩‾㸊⡜㌷㙜㌷㝜〰ぐづばぴどつづぜ〴ぜ〰ぃとちひちっぴづひどぺちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱ Item: Title: ぐづばぴどつづぜ〴ぜ〰ぃとちひちっぴづひどぺちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱ Children: Item: Title: ぐづばぴどつづぜ〴ぜ〰〭ぃぃぜ〴ぜ〰ぜ〵ぜ〰〴ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸲ Item: Title: ぐづばぴどつづぜ〴ぜ〰〭ぃぃぜ〴ぜ〰ぜ〵ぜ〰〵ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸳ Item: Title: ぐづばぴどつづぜ〴ぜ〰ぃうぜ〲㍜〰ぃぃぜ〴ぜ〰ぜ〵ぜ〰〶ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸴ Item: Title: ぐづばぴどつづぜ〴ぜ〰ぃうぜ〲㍜〰ぃぃぜ〴ぜ〰ぜ〵ぜ〰〷ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸵ Item: Title: ぐづばぴどつづぜ〴ぜ〰〭ぃごぜ〴ぜ〰ぜ〵ぜ〰〸ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸶ Item: Title: ぐづばぴどつづぜ〴ぜ〰〭ぃごぜ〴ぜ〰ぜ〵ぜ〰〹ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸷ Item: Title: ぐづばぴどつづぜ〴ぜ〰ぃうぜ〲㍜〰ぃごぜ〴ぜ〰ぜ〵ぜ〰〱〰ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸸ Item: Title: ぐづばぴどつづぜ〴ぜ〰ぃうぜ〲㍜〰ぃごぜ〴ぜ〰ぜ〵ぜ〰〱〱ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸹ Item: Title: ごぁご〴〸ぜ〲㍜〰〵〷ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱〩‾㸊⡜㌷㙜㌷㝜〰ごぁご〴〸ぜ〲㍜〰〵〷〭ぃうぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱ㄩ‾㸊⡜㌷㙜㌷㝜〰ぐづばぴどつづぜ〴ぜ〰ぜ〵ぜ〰〱〲ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱㈩‾㸊⡜㌷㙜㌷㝜〰ぐづばぴどつづぜ〴ぜ〰ぜ〵ぜ〰〱〳ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱㌩‾㸊⡜㌷㙜㌷㝜〰ごぁご〴〸ぜ〲㍜〰〵〷〭ぃべびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱㐩‾㸊⡜㌷㙜㌷㝜〰ぃはのなふでちぴづぜ〴ぜ〰いはへ〭ぜ〴ぜ〰〭ぃぃぜ〴ぜ〰ぜ〵ぜ〰〱〵ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱㔩‾㸊⡜㌷㙜㌷㝜〰ぃはのなふでちぴづぜ〴ぜ〰いはへ〭ぜ〴ぜ〰〭ぃごぜ〴ぜ〰ぜ〵ぜ〰〱〶ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱㘩‾㸊⡜㌷㙜㌷㝜〰いはへ〭ごぁご〴〸ぜ〲㍜〰〵〷ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㜩‾㸊⡜㌷㙜㌷㝜〰ぃづぬぬふぬちひぜ〴ぜ〰ざどちぢどぬどぴべ〬ぜ〴ぜ〰ぉのぴづひのちぬどぺちぴどはの〬ぜ〴ぜ〰ちのつぜ〴ぜ〰がはっちぬどぺちぴどはのぜ〴ぜ〰ぅへばづひどねづのぴびぜ〴ぜ〰ぷどぴとぜ〴ぜ〰えづがちぜ〴ぜ〰ぃづぬぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸷⸱ Item: Title: ごぁご〴〸ぜ〲㍜〰〵〷〭ぃうぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱ㄩ‾㸊⡜㌷㙜㌷㝜〰ぐづばぴどつづぜ〴ぜ〰ぜ〵ぜ〰〱〲ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱㈩‾㸊⡜㌷㙜㌷㝜〰ぐづばぴどつづぜ〴ぜ〰ぜ〵ぜ〰〱〳ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱㌩‾㸊⡜㌷㙜㌷㝜〰ごぁご〴〸ぜ〲㍜〰〵〷〭ぃべびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱㐩‾㸊⡜㌷㙜㌷㝜〰ぃはのなふでちぴづぜ〴ぜ〰いはへ〭ぜ〴ぜ〰〭ぃぃぜ〴ぜ〰ぜ〵ぜ〰〱〵ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱㔩‾㸊⡜㌷㙜㌷㝜〰ぃはのなふでちぴづぜ〴ぜ〰いはへ〭ぜ〴ぜ〰〭ぃごぜ〴ぜ〰ぜ〵ぜ〰〱〶ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱㘩‾㸊⡜㌷㙜㌷㝜〰いはへ〭ごぁご〴〸ぜ〲㍜〰〵〷ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㜩‾㸊⡜㌷㙜㌷㝜〰ぃづぬぬふぬちひぜ〴ぜ〰ざどちぢどぬどぴべ〬ぜ〴ぜ〰ぉのぴづひのちぬどぺちぴどはの〬ぜ〴ぜ〰ちのつぜ〴ぜ〰がはっちぬどぺちぴどはのぜ〴ぜ〰ぅへばづひどねづのぴびぜ〴ぜ〰ぷどぴとぜ〴ぜ〰えづがちぜ〴ぜ〰ぃづぬぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸷⸱ Item: Title: ぐづばぴどつづぜ〴ぜ〰ぜ〵ぜ〰〱〲ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱㈩‾㸊⡜㌷㙜㌷㝜〰ぐづばぴどつづぜ〴ぜ〰ぜ〵ぜ〰〱〳ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱㌩‾㸊⡜㌷㙜㌷㝜〰ごぁご〴〸ぜ〲㍜〰〵〷〭ぃべびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱㐩‾㸊⡜㌷㙜㌷㝜〰ぃはのなふでちぴづぜ〴ぜ〰いはへ〭ぜ〴ぜ〰〭ぃぃぜ〴ぜ〰ぜ〵ぜ〰〱〵ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱㔩‾㸊⡜㌷㙜㌷㝜〰ぃはのなふでちぴづぜ〴ぜ〰いはへ〭ぜ〴ぜ〰〭ぃごぜ〴ぜ〰ぜ〵ぜ〰〱〶ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱㘩‾㸊⡜㌷㙜㌷㝜〰いはへ〭ごぁご〴〸ぜ〲㍜〰〵〷ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㜩‾㸊⡜㌷㙜㌷㝜〰ぃづぬぬふぬちひぜ〴ぜ〰ざどちぢどぬどぴべ〬ぜ〴ぜ〰ぉのぴづひのちぬどぺちぴどはの〬ぜ〴ぜ〰ちのつぜ〴ぜ〰がはっちぬどぺちぴどはのぜ〴ぜ〰ぅへばづひどねづのぴびぜ〴ぜ〰ぷどぴとぜ〴ぜ〰えづがちぜ〴ぜ〰ぃづぬぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸷⸱ Item: Title: ぐづばぴどつづぜ〴ぜ〰ぜ〵ぜ〰〱〳ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱㌩‾㸊⡜㌷㙜㌷㝜〰ごぁご〴〸ぜ〲㍜〰〵〷〭ぃべびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱㐩‾㸊⡜㌷㙜㌷㝜〰ぃはのなふでちぴづぜ〴ぜ〰いはへ〭ぜ〴ぜ〰〭ぃぃぜ〴ぜ〰ぜ〵ぜ〰〱〵ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱㔩‾㸊⡜㌷㙜㌷㝜〰ぃはのなふでちぴづぜ〴ぜ〰いはへ〭ぜ〴ぜ〰〭ぃごぜ〴ぜ〰ぜ〵ぜ〰〱〶ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱㘩‾㸊⡜㌷㙜㌷㝜〰いはへ〭ごぁご〴〸ぜ〲㍜〰〵〷ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㜩‾㸊⡜㌷㙜㌷㝜〰ぃづぬぬふぬちひぜ〴ぜ〰ざどちぢどぬどぴべ〬ぜ〴ぜ〰ぉのぴづひのちぬどぺちぴどはの〬ぜ〴ぜ〰ちのつぜ〴ぜ〰がはっちぬどぺちぴどはのぜ〴ぜ〰ぅへばづひどねづのぴびぜ〴ぜ〰ぷどぴとぜ〴ぜ〰えづがちぜ〴ぜ〰ぃづぬぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸷⸱ Item: Title: ごぁご〴〸ぜ〲㍜〰〵〷〭ぃべびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱㐩‾㸊⡜㌷㙜㌷㝜〰ぃはのなふでちぴづぜ〴ぜ〰いはへ〭ぜ〴ぜ〰〭ぃぃぜ〴ぜ〰ぜ〵ぜ〰〱〵ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱㔩‾㸊⡜㌷㙜㌷㝜〰ぃはのなふでちぴづぜ〴ぜ〰いはへ〭ぜ〴ぜ〰〭ぃごぜ〴ぜ〰ぜ〵ぜ〰〱〶ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱㘩‾㸊⡜㌷㙜㌷㝜〰いはへ〭ごぁご〴〸ぜ〲㍜〰〵〷ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㜩‾㸊⡜㌷㙜㌷㝜〰ぃづぬぬふぬちひぜ〴ぜ〰ざどちぢどぬどぴべ〬ぜ〴ぜ〰ぉのぴづひのちぬどぺちぴどはの〬ぜ〴ぜ〰ちのつぜ〴ぜ〰がはっちぬどぺちぴどはのぜ〴ぜ〰ぅへばづひどねづのぴびぜ〴ぜ〰ぷどぴとぜ〴ぜ〰えづがちぜ〴ぜ〰ぃづぬぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸷⸱ Item: Title: ぃはのなふでちぴづぜ〴ぜ〰いはへ〭ぜ〴ぜ〰〭ぃぃぜ〴ぜ〰ぜ〵ぜ〰〱〵ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱㔩‾㸊⡜㌷㙜㌷㝜〰ぃはのなふでちぴづぜ〴ぜ〰いはへ〭ぜ〴ぜ〰〭ぃごぜ〴ぜ〰ぜ〵ぜ〰〱〶ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱㘩‾㸊⡜㌷㙜㌷㝜〰いはへ〭ごぁご〴〸ぜ〲㍜〰〵〷ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㜩‾㸊⡜㌷㙜㌷㝜〰ぃづぬぬふぬちひぜ〴ぜ〰ざどちぢどぬどぴべ〬ぜ〴ぜ〰ぉのぴづひのちぬどぺちぴどはの〬ぜ〴ぜ〰ちのつぜ〴ぜ〰がはっちぬどぺちぴどはのぜ〴ぜ〰ぅへばづひどねづのぴびぜ〴ぜ〰ぷどぴとぜ〴ぜ〰えづがちぜ〴ぜ〰ぃづぬぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸷⸱ Item: Title: ぃはのなふでちぴづぜ〴ぜ〰いはへ〭ぜ〴ぜ〰〭ぃごぜ〴ぜ〰ぜ〵ぜ〰〱〶ぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸶⸱㘩‾㸊⡜㌷㙜㌷㝜〰いはへ〭ごぁご〴〸ぜ〲㍜〰〵〷ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㜩‾㸊⡜㌷㙜㌷㝜〰ぃづぬぬふぬちひぜ〴ぜ〰ざどちぢどぬどぴべ〬ぜ〴ぜ〰ぉのぴづひのちぬどぺちぴどはの〬ぜ〴ぜ〰ちのつぜ〴ぜ〰がはっちぬどぺちぴどはのぜ〴ぜ〰ぅへばづひどねづのぴびぜ〴ぜ〰ぷどぴとぜ〴ぜ〰えづがちぜ〴ぜ〰ぃづぬぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸷⸱ Item: Title: いはへ〭ごぁご〴〸ぜ〲㍜〰〵〷ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㜩‾㸊⡜㌷㙜㌷㝜〰ぃづぬぬふぬちひぜ〴ぜ〰ざどちぢどぬどぴべ〬ぜ〴ぜ〰ぉのぴづひのちぬどぺちぴどはの〬ぜ〴ぜ〰ちのつぜ〴ぜ〰がはっちぬどぺちぴどはのぜ〴ぜ〰ぅへばづひどねづのぴびぜ〴ぜ〰ぷどぴとぜ〴ぜ〰えづがちぜ〴ぜ〰ぃづぬぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸷⸱ Item: Title: ぃづぬぬふぬちひぜ〴ぜ〰ざどちぢどぬどぴべ〬ぜ〴ぜ〰ぉのぴづひのちぬどぺちぴどはの〬ぜ〴ぜ〰ちのつぜ〴ぜ〰がはっちぬどぺちぴどはのぜ〴ぜ〰ぅへばづひどねづのぴびぜ〴ぜ〰ぷどぴとぜ〴ぜ〰えづがちぜ〴ぜ〰ぃづぬぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸷⸱ Children: Item: Title: えづがちぜ〴ぜ〰ぃづぬぬびぜ〴ぜ〰ぃふぬぴふひづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸷⸲ Item: Title: ぃづぬぬふぬちひぜ〴ぜ〰ざどちぢどぬどぴべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸷⸳ Item: Title: ぐづばぴどつづぜ〴ぜ〰ぉのぴづひのちぬどぺちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㠩‾㸊⡜㌷㙜㌷㝜〰ぃづぬぬふぬちひぜ〴ぜ〰ざどちぢどぬどぴべ〬ぜ〴ぜ〰ぉのぴづひのちぬどぺちぴどはのぜ〴ぜ〰ちのつぜ〴ぜ〰がはっちぬどぺちぴどはのぜ〴ぜ〰ぅへばづひどねづのぴびぜ〴ぜ〰ぷどぴとぜ〴ぜ〰がづどびとねちのどちぜ〴ぜ〰ぐちひちびどぴづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸸⸱ Item: Title: ぃづぬぬふぬちひぜ〴ぜ〰ざどちぢどぬどぴべ〬ぜ〴ぜ〰ぉのぴづひのちぬどぺちぴどはのぜ〴ぜ〰ちのつぜ〴ぜ〰がはっちぬどぺちぴどはのぜ〴ぜ〰ぅへばづひどねづのぴびぜ〴ぜ〰ぷどぴとぜ〴ぜ〰がづどびとねちのどちぜ〴ぜ〰ぐちひちびどぴづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸸⸱ Children: Item: Title: ぃづぬぬふぬちひぜ〴ぜ〰ざどちぢどぬどぴべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸸⸲ Item: Title: ぐづばぴどつづぜ〴ぜ〰さばぴちにづぜ〴ぜ〰てはひぜ〴ぜ〰がづどびとねちのどちぜ〴ぜ〰つはのはぶちのどぜ〴ぜ〰ぐひはねちびぴどではぴづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸸⸳ Item: Title: ぉのぴひちっづぬぬふぬちひぜ〴ぜ〰がはっちぬどぺちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ぴとづぜ〴ぜ〰ぉのぴづひのちぬどぺづつぜ〴ぜ〰ぐづばぴどつづびぜ〴ぜ〰どのぜ〴ぜ〰がづどびとねちのどちぜ〴ぜ〰つはのはぶちのどぜ〴ぜ〰ぐひはねちびぴどではぴづびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㤩‾㸊⡜㌷㙜㌷㝜〰ぃどひっふぬちひぜ〴ぜ〰いどっとひはどびねぜ〴ぜ〰ぜ〵ぜ〰ぃいぜ〵ㅜ〰ぜ〴ぜ〰こばづっぴひはびっはばべぜ〴ぜ〰いづぴちどぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㄰ Item: Title: ぃどひっふぬちひぜ〴ぜ〰いどっとひはどびねぜ〴ぜ〰ぜ〵ぜ〰ぃいぜ〵ㅜ〰ぜ〴ぜ〰こばづっぴひはびっはばべぜ〴ぜ〰いづぴちどぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㄰ Item: Title: ぃはねばふぴちぴどはのちぬぜ〴ぜ〰いづぴちどぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: ぃはのっぬふびどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: 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