title: Synthetic Peptides as Protein Mimics.
abstract: The design and generation of molecules capable of mimicking the binding and/or functional sites of proteins represents a promising strategy for the exploration and modulation of protein function through controlled interference with the underlying molecular interactions. Synthetic peptides have proven an excellent type of molecule for the mimicry of protein sites because such peptides can be generated as exact copies of protein fragments, as well as in diverse chemical modifications, which includes the incorporation of a large range of non-proteinogenic amino acids as well as the modification of the peptide backbone. Apart from extending the chemical and structural diversity presented by peptides, such modifications also increase the proteolytic stability of the molecules, enhancing their utility for biological applications. This article reviews recent advances by this and other laboratories in the use of synthetic protein mimics to modulate protein function, as well as to provide building blocks for synthetic biology.
authors.affiliation: Department of Chemistry and Pharmacy, University of Erlangen-Nuremberg , Erlangen , Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Groß
authors.affiliation: Department of Chemistry and Pharmacy, University of Erlangen-Nuremberg , Erlangen , Germany.
authors.forename: Chie
authors.initials: C
authors.lastname: Hashimoto
authors.affiliation: Institute of Biochemistry, University of Erlangen-Nuremberg , Erlangen , Germany.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Sticht
authors.affiliation: Department of Chemistry and Pharmacy, University of Erlangen-Nuremberg , Erlangen , Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Eichler
keywords: biomaterials; peptides; protein mimics; protein–protein interactions; structure-based design
references.citation: Discov Med. 2013 Mar;15(82):166-76
references.pmid: 23545045
references.citation: Biochemistry. 2013 Sep 3;52(35):6108-13
references.pmid: 23919461
references.citation: ACS Biomater Sci Eng. 2015 Jun 8;1(6):431-439
references.pmid: 26240838
references.citation: Chem Soc Rev. 2011 Aug;40(8):4422-37
references.pmid: 21483974
references.citation: J Org Chem. 2002 May 3;67(9):3057-64
references.pmid: 11975567
references.citation: Nat Rev Immunol. 2010 Jul;10(7):527-35
references.pmid: 20577269
references.citation: Science. 2010 Feb 19;327(5968):1010-3
references.pmid: 20167788
references.citation: Angew Chem Int Ed Engl. 2002 Oct 18;41(20):3863-5
references.pmid: 12386872
references.citation: Proc Natl Acad Sci U S A. 2013 Sep 3;110(36):E3445-54
references.pmid: 23946421
references.citation: J Am Chem Soc. 2002 Dec 18;124(50):14917-21
references.pmid: 12475333
references.citation: J Biol Chem. 2010 Dec 3;285(49):38580-9
references.pmid: 20843795
references.citation: Expert Opin Emerg Drugs. 2015;20(4):531-6
references.pmid: 26583759
references.citation: Angew Chem Int Ed Engl. 2014 Feb 24;53(9):2498-503
references.pmid: 24481744
references.citation: Org Biomol Chem. 2014 Apr 28;12(16):2606-14
references.pmid: 24637609
references.citation: Chembiochem. 2011 Jan 3;12(1):100-9
references.pmid: 21132689
references.citation: Bioorg Med Chem. 2005 Mar 15;13(6):2055-64
references.pmid: 15727859
references.citation: Cold Spring Harb Perspect Med. 2012 Aug 01;2(8):
references.pmid: 22908191
references.citation: Drug Discov Today. 2015 Jan;20(1):122-8
references.pmid: 25450771
references.citation: Int J Cancer. 2008 May 15;122(10):2351-9
references.pmid: 18224686
references.citation: Acc Chem Res. 2005 Jun;38(6):486-93
references.pmid: 15966715
references.citation: Eur J Biochem. 2003 Sep;270(18):3657-66
references.pmid: 12950249
references.citation: Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):2794-9
references.pmid: 18287037
references.citation: Amino Acids. 2011 Feb;40(2):731-40
references.pmid: 20683629
references.citation: ChemMedChem. 2012 Feb 6;7(2):205-8
references.pmid: 22247043
references.citation: Mol Cancer Ther. 2009 Sep;8(9):2708-17
references.pmid: 19706734
references.citation: J Am Chem Soc. 2014 Sep 10;136(36):12682-90
references.pmid: 25068693
references.citation: Org Lett. 2001 Nov 1;3(22):3499-502
references.pmid: 11678692
references.citation: Angew Chem Int Ed Engl. 2002 Aug 16;41(16):2937-40
references.pmid: 12203417
references.citation: J Biol Chem. 2009 May 1;284(18):12363-72
references.pmid: 19251703
references.citation: Angew Chem Int Ed Engl. 2007;46(8):1253-5
references.pmid: 17211914
references.citation: J Am Chem Soc. 2012 Apr 11;134(14):6210-7
references.pmid: 22413859
references.citation: J Pept Res. 2005 Feb;65(2):229-60
references.pmid: 15705167
references.citation: Science. 2010 Nov 19;330(6007):1066-71
references.pmid: 20929726
references.citation: Nature. 2013 Jul 25;499(7459):438-43
references.pmid: 23863939
references.citation: Bioorg Med Chem Lett. 2004 Mar 22;14(6):1403-6
references.pmid: 15006371
references.citation: ACS Chem Biol. 2013 Mar 15;8(3):506-12
references.pmid: 23214419
references.citation: Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11273-8
references.pmid: 13679575
references.citation: Nat Rev Mol Cell Biol. 2001 Feb;2(2):127-37
references.pmid: 11252954
references.citation: Chem Biol Drug Des. 2013 Jan;81(1):136-47
references.pmid: 23253135
references.citation: J Biol Chem. 2008 Apr 25;283(17):11126-34
references.pmid: 18303020
references.citation: J Clin Invest. 2012 Jun;122(6):2018-31
references.pmid: 22622039
references.citation: Nature. 1990 Nov 8;348(6297):125-32
references.pmid: 2122258
references.citation: J Am Chem Soc. 2011 Sep 14;133(36):14220-3
references.pmid: 21846146
references.citation: Curr Med Chem. 1998 Feb;5(1):29-62
references.pmid: 9481033
references.citation: Clin Cancer Res. 1999 Nov;5(11):3645-52
references.pmid: 10589782
references.citation: Chembiochem. 2014 Feb 10;15(3):451-9
references.pmid: 24382674
references.citation: Chemistry. 2012 Jul 2;18(27):8292-5
references.pmid: 22692798
references.citation: PLoS One. 2015 Mar 19;10(3):e0118796
references.pmid: 25790232
references.citation: Nucleic Acids Res. 2000 Jan 1;28(1):235-42
references.pmid: 10592235
references.citation: J Pept Sci. 2013 Mar;19(3):127-40
references.pmid: 23349031
references.citation: Nature. 2014 Oct 23;514(7523):455-61
references.pmid: 25296255
references.citation: Science. 2013 Sep 20;341(6152):1387-90
references.pmid: 24030490
references.citation: Acc Chem Res. 2008 Oct;41(10):1366-75
references.pmid: 18578513
references.citation: Nat Med. 2004 Aug;10(8):789-99
references.pmid: 15286780
references.citation: J Am Chem Soc. 2003 Aug 13;125(32):9821-7
references.pmid: 12904048
references.citation: Cell. 1997 Apr 18;89(2):263-73
references.pmid: 9108481
references.citation: Proc Natl Acad Sci U S A. 2005 Sep 6;102(36):12903-8
references.pmid: 16129831
references.citation: Nat Rev Drug Discov. 2007 Jul;6(7):541-55
references.pmid: 17585331
references.citation: J Med Chem. 2012 Feb 9;55(3):1137-46
references.pmid: 22196480
references.citation: Curr Opin Chem Biol. 2011 Jun;15(3):427-34
references.pmid: 21507707
references.citation: Cancer Res. 1996 Feb 15;56(4):880-5
references.pmid: 8631028
references.citation: Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10537-41
references.pmid: 1438243
references.citation: Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9770-4
references.pmid: 7937889
references.citation: J Am Chem Soc. 2006 Mar 22;128(11):3496-7
references.pmid: 16536504
references.citation: Chem Biol. 1996 Jul;3(7):543-50
references.pmid: 8807886
references.citation: N Engl J Med. 2003 May 29;348(22):2175-85
references.pmid: 12637625
references.citation: Angew Chem Int Ed Engl. 2014 Jul 1;53(27):6866-81
references.pmid: 24920517
references.citation: J Immunol Methods. 2002 Sep 1;267(1):13-26
references.pmid: 12135797
references.citation: J Am Chem Soc. 2003 Jan 29;125(4):935-9
references.pmid: 12537491
references.citation: J Med Chem. 1999 Sep 23;42(19):3743-78
references.pmid: 10508425
references.citation: Bioorg Med Chem. 1999 Jan;7(1):161-75
references.pmid: 10199666
references.citation: Bioconjug Chem. 2010 Apr 21;21(4):709-14
references.pmid: 20359196
references.citation: Curr Top Med Chem. 2011 Dec;11(24):2959-84
references.pmid: 22044229
references.citation: Nature. 1998 Jun 18;393(6686):648-59
references.pmid: 9641677
references.citation: Soft Matter. 2006 Sep 19;2(10):822-835
references.pmid: 32680274
references.citation: Physiol Rev. 2013 Jan;93(1):269-309
references.pmid: 23303910
references.citation: Beilstein J Org Chem. 2012;8:1858-66
references.pmid: 23209523
references.citation: Drug Discov Today. 2013 Sep;18(17-18):807-17
references.pmid: 23726889
references.citation: Science. 2012 Jul 13;337(6091):183-6
references.pmid: 22798606
references.citation: Proc Natl Acad Sci U S A. 2015 Feb 17;112(7):2011-6
references.pmid: 25646443
references.citation: Methods Enzymol. 2013;523:407-29
references.pmid: 23422441
references.citation: Chembiochem. 2015 Feb 9;16(3):446-54
references.pmid: 25639621
references.citation: Biochemistry. 1995 Jan 24;34(3):984-90
references.pmid: 7827056
references.citation: Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14664-9
references.pmid: 12417739
references.citation: Science. 2013 Feb 22;339(6122):971-5
references.pmid: 23430657
references.citation: ACS Nano. 2013 Jun 25;7(6):4715-32
references.pmid: 23721608
references.citation: Angew Chem Int Ed Engl. 2002 Jul 15;41(14):2596-9
references.pmid: 12203546
references.citation: Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):3053-8
references.pmid: 10077635
references.citation: ACS Chem Biol. 2013 Oct 18;8(10):2235-44
references.pmid: 23898787
references.citation: Nat Chem Biol. 2011 Jul 17;7(9):585-7
references.pmid: 21765406
references.citation: J Am Chem Soc. 2002 Apr 3;124(13):3284-91
references.pmid: 11916412
references.citation: Chembiochem. 2005 May;6(5):821-4
references.pmid: 15812852
references.citation: J Amino Acids. 2012;2012:967347
references.pmid: 23316341
references.citation: Angew Chem Int Ed Engl. 2008;47(19):3642-5
references.pmid: 18383498
references.citation: N Engl J Med. 2003 May 29;348(22):2228-38
references.pmid: 12773651
references.citation: Science. 1985 Jun 14;228(4705):1315-7
references.pmid: 4001944
references.citation: J Am Chem Soc. 2013 Jul 3;135(26):9777-84
references.pmid: 23750583
references.citation: Nat Rev Drug Discov. 2011 Dec 16;11(1):37-51
references.pmid: 22173434
references.citation: Appl Microbiol Biotechnol. 2010 Jan;85(4):909-19
references.pmid: 19885657
references.citation: Acc Chem Res. 2008 Oct;41(10):1278-88
references.pmid: 18412373
references.citation: Proc Natl Acad Sci U S A. 2010 Jun 8;107(23):10655-60
references.pmid: 20483992
references.citation: Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9367-71
references.pmid: 1409642
references.citation: J Am Chem Soc. 2007 Mar 7;129(9):2548-58
references.pmid: 17295482
references.citation: Expert Opin Drug Deliv. 2016;13(3):373-87
references.pmid: 26634750
references.citation: FEBS Lett. 2008 Apr 2;582(7):1141-6
references.pmid: 18339322
references.citation: Proc Natl Acad Sci U S A. 2011 Mar 8;108(10):3952-7
references.pmid: 21325613
references.citation: Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13091-6
references.pmid: 10557278
references.citation: Methods Enzymol. 2012;503:3-33
references.pmid: 22230563
references.citation: Bioorg Med Chem Lett. 2011 Mar 1;21(5):1472-5
references.pmid: 21277201
references.citation: Bioorg Med Chem. 2015 Jul 15;23(14):4050-5
references.pmid: 25801155
references.citation: J Mol Recognit. 2010 Nov-Dec;23(6):559-68
references.pmid: 21038356
references.citation: Angew Chem Int Ed Engl. 2015 Jul 27;54(31):8896-927
references.pmid: 26119925
references.citation: J Pept Sci. 2014 Nov;20(11):831-6
references.pmid: 25092519
references.citation: Annu Rev Biochem. 2011;80:189-210
references.pmid: 21370981
references.citation: Proc Natl Acad Sci U S A. 2008 Jul 1;105(26):9029-34
references.pmid: 18574150
references.citation: Antimicrob Agents Chemother. 2015 Jul;59(7):4112-20
references.pmid: 25941221
references.citation: AIDS Res Hum Retroviruses. 1997 Dec 10;13(18):1549-59
references.pmid: 9430247
references.citation: J Am Chem Soc. 2003 Oct 1;125(39):11802-3
references.pmid: 14505386
references.citation: J Med Chem. 2014 Aug 14;57(15):6275-88
references.pmid: 24601557
references.citation: Chembiochem. 2011 Dec 16;12(18):2829-36
references.pmid: 22076829
references.citation: Chembiochem. 2006 Jun;7(6):868-78
references.pmid: 16642526
references.citation: Front Immunol. 2013 Sep 03;4:257
references.pmid: 24027570
references.citation: Curr Opin Mol Ther. 2009 Jun;11(3):299-307
references.pmid: 19479663
references.citation: Nat Biotechnol. 2003 Jan;21(1):71-6
references.pmid: 12483221
references.citation: J Am Chem Soc. 2015 Aug 26;137(33):10554-62
references.pmid: 26219086
references.citation: Curr Opin Chem Biol. 2008 Dec;12(6):707-13
references.pmid: 18935974
references.citation: Biopolymers. 2007;88(5):746-53
references.pmid: 17427180
references.citation: Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12303-8
references.pmid: 9356444
references.citation: Protein Eng. 2000 Jun;13(6):385-9
references.pmid: 10877847
references.citation: J Am Chem Soc. 2011 Mar 16;133(10):3230-3
references.pmid: 21341746
references.citation: Biomacromolecules. 2009 Sep 14;10(9):2619-25
references.pmid: 19663418
references.citation: Infect Immun. 2000 Oct;68(10):5908-13
references.pmid: 10992501
references.citation: Cold Spring Harb Perspect Med. 2012 Apr;2(4):a007161
references.pmid: 22474613
references.citation: J Am Chem Soc. 2009 Jun 3;131(21):7353-9
references.pmid: 19432477
references.citation: J Mol Biol. 2005 Nov 4;353(4):859-72
references.pmid: 16213522
references.citation: J Am Chem Soc. 2001 Jul 4;123(26):6451-2
references.pmid: 11427086
references.citation: J Am Chem Soc. 2005 Dec 7;127(48):17025-9
references.pmid: 16316249
references.citation: Biochem Biophys Res Commun. 2009 May 8;382(3):540-4
references.pmid: 19289098
references.citation: Angew Chem Int Ed Engl. 1998 Dec 17;37(23):3281-3284
references.pmid: 29711420
references.citation: Chembiochem. 2002 Nov 4;3(11):1126-33
references.pmid: 12404639
references.citation: Chem Commun (Camb). 2009 Feb 21;(7):821-3
references.pmid: 19322453
references.citation: Chem Biodivers. 2004 Aug;1(8):1111-239
references.pmid: 17191902
references.citation: J Biol Chem. 2009 Dec 4;284(49):34126-34
references.pmid: 19808684
references.citation: J Immunol. 2004 Jun 1;172(11):6994-7001
references.pmid: 15153520
references.citation: BMC Immunol. 2009 Mar 11;10:13
references.pmid: 19284584
references.citation: Chem Rev. 2001 Oct;101(10):3219-32
references.pmid: 11710070
references.citation: Biochem Pharmacol. 1999 Dec 1;58(11):1775-80
references.pmid: 10571252
references.citation: Ann Med. 1998 Apr;30(2):176-85
references.pmid: 9667796