title: A readily applicable strategy to convert peptides to peptoid-based therapeutics.
abstract: Incorporation of unnatural amino acids and peptidomimetic residues into therapeutic peptides is highly efficacious and commonly employed, but generally requires laborious trial-and-error approaches. Previously, we demonstrated that C20 peptide has the potential to be a potential antiviral agent. Herein we report our attempt to improve the biological properties of this peptide by introducing peptidomimetics. Through combined alanine, proline, and sarcosine scans coupled with a competitive fluorescence polarization assay developed for identifying antiviral peptides, we enabled to pinpoint peptoid-tolerant peptide residues within C20 peptide. The synergistic benefits of combining these (and other) commonly employed methods could lead to a easily applicable strategy for designing and refining therapeutically-attractive peptidomimetics.
authors.affiliation: Department of Chemical and Systems Biology, School of Medicine, Stanford University, Stanford, California, USA.
authors.forename: Minyoung
authors.initials: M
authors.lastname: Park
authors.forename: Modi
authors.initials: M
authors.lastname: Wetzler
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Jardetzky
authors.forename: Annelise E
authors.initials: AE
authors.lastname: Barron
mesh_terms: D000409:Alanine / Q000737:chemistry; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000596:Amino Acids / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D034444:Peptoids / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D011392:Proline / Q000737:chemistry; D012521:Sarcosine / Q000737:chemistry
chemical_list: D000596:Amino Acids; D010455:Peptides; D034444:Peptoids; D011392:Proline; D000409:Alanine; D012521:Sarcosine
references.citation: Plant Cell Physiol. 2011 Jan;52(1):30-6
references.pmid: 20926417
references.citation: Drug Discov Today. 2010 Jan;15(1-2):40-56
references.pmid: 19879957
references.citation: Antivir Ther. 2005;10(7):833-40
references.pmid: 16312179
references.citation: Biochemistry. 1995 Jan 24;34(3):724-30
references.pmid: 7827029
references.citation: Biochemistry. 2006 Oct 31;45(43):13007-17
references.pmid: 17059217
references.citation: Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14664-9
references.pmid: 12417739
references.citation: Chem Soc Rev. 2007 Aug;36(8):1249-62
references.pmid: 17619685
references.citation: Trends Biotechnol. 2009 Nov;27(11):628-35
references.pmid: 19766335
references.citation: ACS Chem Biol. 2011 Dec 16;6(12):1367-74
references.pmid: 21958072
references.citation: Curr Pharm Des. 2011;17(25):2732-47
references.pmid: 21728985
references.citation: Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4309-14
references.pmid: 9539733
references.citation: Proc Natl Acad Sci U S A. 2009 Nov 17;106(46):19375-80
references.pmid: 19880740
references.citation: Bioorg Med Chem. 2009 Feb 1;17(3):959-66
references.pmid: 18343124
references.citation: Biochem Biophys Res Commun. 2003 Mar 14;302(3):469-75
references.pmid: 12615056
references.citation: Science. 2001 Feb 2;291(5505):884-8
references.pmid: 11229405
references.citation: Chembiochem. 2001 Mar 2;2(3):171-9
references.pmid: 11828442
references.citation: Curr Opin Chem Biol. 2008 Jun;12(3):292-6
references.pmid: 18423417
references.citation: Bioorg Med Chem Lett. 2008 Nov 15;18(22):5892-4
references.pmid: 18653335
references.citation: Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):2794-9
references.pmid: 18287037
references.citation: J Pept Sci. 2007 Aug;13(8):529-35
references.pmid: 17604338
references.citation: Cell. 2011 Jan 7;144(1):132-42
references.pmid: 21215375
references.citation: J Pept Sci. 2009 Jul;15(7):451-4
references.pmid: 19455541
references.citation: Molecules. 2010 Aug 04;15(8):5282-335
references.pmid: 20714299
references.citation: J Biol Chem. 2003 Sep 19;278(38):36810-8
references.pmid: 12857736
references.citation: J Org Chem. 2009 Apr 17;74(8):2964-74
references.pmid: 19309103
references.citation: Chembiochem. 2009 Oct 12;10(15):2504-12
references.pmid: 19739189
references.citation: Protein Eng. 2000 Sep;13(9):603-6
references.pmid: 11054453
references.citation: Curr Opin Biotechnol. 2006 Dec;17(6):638-42
references.pmid: 17049837
references.citation: Crit Rev Biochem Mol Biol. 1993;28(1):31-81
references.pmid: 8444042
references.citation: Nat Chem Biol. 2010 Mar;6(3):162-165
references.pmid: 20154660
references.citation: Nat Struct Biol. 1996 Aug;3(8):682-7
references.pmid: 8756326
references.citation: Science. 1989 Jun 2;244(4908):1081-5
references.pmid: 2471267
references.citation: FASEB J. 1995 Jun;9(9):736-44
references.pmid: 7601338
references.citation: Protein Pept Lett. 2006;13(8):829-33
references.pmid: 17073730
references.citation: Nat Struct Biol. 2001 May;8(5):380-1
references.pmid: 11323705
references.citation: Curr Opin Mol Ther. 2009 Jun;11(3):299-307
references.pmid: 19479663
references.citation: Anal Biochem. 2011 Feb 15;409(2):195-201
references.pmid: 20971054
references.citation: Methods Mol Biol. 2008;494:1-8
references.pmid: 18726565
references.citation: J Pept Sci. 2010 Sep;16(9):480-5
references.pmid: 20629116
references.citation: Chem Biol. 2000 Jul;7(7):463-73
references.pmid: 10903934
references.citation: J Org Chem. 2008 Aug 1;73(15):5663-74
references.pmid: 18489158
references.citation: Prog Biophys Mol Biol. 1995;64(1):1-54
references.pmid: 8868522