e24c2088b2c87075e455d3d8471ebd51 pmc_9495681.pdf fb1ad5bfa92b6d5a09872c08b43b4e6f3f77e070 pmc_9495681.pdf 621d2e524fb011f96b8221a152e91afa624c55df2e9a51487996f8da4d56a7a3 pmc_9495681.pdf Title: Examining Topoisomers of a Snake-Venom-Derived Peptide for Improved Antimicrobial and Antitumoral Properties Subject: Ctn[15-34], the C-terminal section of crotalicidin (Ctn), a cathelicidin from a South American pit viper, is an antimicrobial and antitumoral peptide with remarkably longer stability in human serum than the parent Ctn. In this work, a set of topoisomers of both Ctn and Ctn[15-34], including the retro, enantio, and retroenantio versions, were synthesized and tested to investigate the structural requirements for activity. All topoisomers were as active as the cognate sequences against Gram-negative bacteria and tumor cells while slightly more toxic towards normal cells. More importantly, the enhanced serum stability of the D-amino-acid-containing versions suggests that such topoisomers must be preferentially considered as future antimicrobial and anticancer peptide leads. Keywords: antimicrobial peptides; snake venom; crotalicidin; Ctn[15-34]; enantio-, retro-, and retroenantio peptides; topoisomer peptides; antitumoral peptides Author: Adam Carrera-Aubesart, Sira Defaus, Clara Pérez-Peinado, Daniel Sandín, Marc Torrent, Maria Ángeles Jiménez and David Andreu Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Mon Aug 29 08:33:07 2022 CEST ModDate: Mon Aug 29 08:46:36 2022 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 13 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 9015380 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- YQFJFW+VnURWPalladioL Type 1 Custom yes yes no 10 0 KVNLIS+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 WUWHVF+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 UQMXIM+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 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yes yes 321 0 FNTSBS+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 327 0 FNTSBS+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 333 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-07-01 02:41:18 CEST RepresentationInformation: pmc_9495681.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2022-10-10 02:26:02 CEST Size: 9015380 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 553 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Peptide Synthesis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Peptide Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Peptide Purification Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: NMR Spectroscopy Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: NMR Structure Calculation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Bacterial Strains and MIC Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Cell Culture Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Peptide Cytotoxicity Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Hemolytic Activity Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Serum Stability Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Children: Item: Title: Synthesis of Ctn and Ctn[15-34] Topoisomers Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Minimal Inhibitory Concentration (MIC) Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Cell Viability Studies Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Hemolytic Activity Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Serum Stability Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: NMR Structures of Ctn and Ctn[15-34] Retroenantio Versions in DPC Micelles Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Info: Title: Examining Topoisomers of a Snake-Venom-Derived Peptide for Improved Antimicrobial and Antitumoral Properties Author: Adam Carrera-Aubesart, Sira Defaus, Clara Pérez-Peinado, Daniel Sandín, Marc Torrent, Maria Ángeles Jiménez and David Andreu Subject: Ctn[15-34], the C-terminal section of crotalicidin (Ctn), a cathelicidin from a South American pit viper, is an antimicrobial and antitumoral peptide with remarkably longer stability in human serum than the parent Ctn. In this work, a set of topoisomers of both Ctn and Ctn[15-34], including the retro, enantio, and retroenantio versions, were synthesized and tested to investigate the structural requirements for activity. All topoisomers were as active as the cognate sequences against Gram-negative bacteria and tumor cells while slightly more toxic towards normal cells. More importantly, the enhanced serum stability of the D-amino-acid-containing versions suggests that such topoisomers must be preferentially considered as future antimicrobial and anticancer peptide leads. Keywords: antimicrobial peptides; snake venom; crotalicidin; Ctn[15-34]; enantio-, retro-, and retroenantio peptides; topoisomer peptides; antitumoral peptides Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Mon Aug 29 08:33:07 CEST 2022 ModDate: Mon Aug 29 08:46:36 CEST 2022 ID: 0x1038ac225b2bb1e4ce605e36c3849cfd, 0x1038ac225b2bb1e4ce605e36c3849cfd Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: JHYTSG+CMR10 FontSubset: true FirstChar: 61 LastChar: 61 FontDescriptor: FontName: JHYTSG+CMR10 Flags: Symbolic FontBBox: -40, -250, 1009, 750 FontFile: true Font: BaseFont: FFJGHL+CMSY10 FontSubset: true FirstChar: 0 LastChar: 48 FontDescriptor: FontName: FFJGHL+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true Font: BaseFont: XIRVNA+EURB10 FontSubset: true FirstChar: 22 LastChar: 22 FontDescriptor: FontName: XIRVNA+EURB10 Flags: Symbolic FontBBox: -30, -247, 1178, 723 FontFile: true Font: BaseFont: YQFJFW+VnURWPalladioL FontSubset: 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