Cystine Knot Peptides with Tuneable Activity and Mechanism.
Activity Switch
Enzymes
Inhibitors
Knottins
Photoactivation
Journal
Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543
Informations de publication
Date de publication:
02 05 2022
02 05 2022
Historique:
received:
19
01
2022
pubmed:
1
3
2022
medline:
27
4
2022
entrez:
28
2
2022
Statut:
ppublish
Résumé
Knottins are topologically complex peptides that are stabilised by a cystine knot and have exceptionally diverse functions, including protease inhibition. However, approaches for tuning their activity in situ are limited. Here, we demonstrate separate approaches for tuning the activity of knottin protease inhibitors using light or streptavidin. We show that the inhibitory activity and selectivity of an engineered knottin can be controlled with light by activating a second mode of action that switches the inhibitor ON against new targets. Guided by a knottin library screen, we also identify a position in the inhibitor's binding loop that permits insertion of a biotin tag without impairing activity. Using streptavidin, biotinylated knottins with nanomolar affinity can be switched OFF in activity assays, and the anticoagulant activity of a factor XIIa inhibitor can be rapidly switched OFF in human plasma. Our findings expand the scope of engineered knottins for precisely controlling protein function.
Identifiants
pubmed: 35224831
doi: 10.1002/anie.202200951
pmc: PMC9539897
doi:
Substances chimiques
Cystine-Knot Miniproteins
0
Peptides
0
Proteins
0
Cystine
48TCX9A1VT
Streptavidin
9013-20-1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e202200951Informations de copyright
© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.
Références
Angew Chem Int Ed Engl. 2011 Aug 8;50(33):7645-9
pubmed: 21648030
Cell. 1988 May 20;53(4):505-18
pubmed: 3286010
Chembiochem. 2014 Sep 22;15(14):2053-7
pubmed: 25125335
Cell Chem Biol. 2020 Mar 19;27(3):306-313.e4
pubmed: 31732432
Angew Chem Int Ed Engl. 2022 May 2;61(19):e202200951
pubmed: 35224831
Org Lett. 2007 Dec 20;9(26):5497-500
pubmed: 18041846
Science. 1994 Nov 4;266(5186):776-9
pubmed: 7973629
Science. 2016 Apr 29;352(6285):575-80
pubmed: 27033546
Angew Chem Int Ed Engl. 2018 Sep 3;57(36):11634-11639
pubmed: 29908104
Angew Chem Int Ed Engl. 2011 Feb 7;50(6):1325-7
pubmed: 21290504
PLoS One. 2013 Oct 11;8(10):e76956
pubmed: 24146945
J Mol Biol. 1999 Dec 17;294(5):1327-36
pubmed: 10600388
Nat Commun. 2015 Jul 22;6:7830
pubmed: 26198003
Proc Natl Acad Sci U S A. 2010 Jan 26;107(4):1361-6
pubmed: 20080559
Nature. 2019 Aug;572(7768):205-210
pubmed: 31341284
J Med Chem. 2009 Oct 22;52(20):6197-200
pubmed: 19772295
Angew Chem Int Ed Engl. 2014 Mar 24;53(13):3392-5
pubmed: 24554486
J Biol Chem. 2013 May 10;288(19):13885-96
pubmed: 23548907
Curr Opin Chem Biol. 2016 Oct;34:143-150
pubmed: 27642714
ACS Chem Biol. 2019 Dec 20;14(12):2833-2840
pubmed: 31750642
ACS Med Chem Lett. 2018 Nov 21;9(12):1258-1262
pubmed: 30613336
Science. 2005 Jul 29;309(5735):755-8
pubmed: 16051792
J Am Chem Soc. 2018 May 2;140(17):5842-5852
pubmed: 29627987
J Mol Biol. 2010 Jan 8;395(1):167-75
pubmed: 19852971
Cell Chem Biol. 2022 Mar 17;29(3):451-462.e8
pubmed: 34774126
Angew Chem Int Ed Engl. 2006 May 5;45(19):3126-30
pubmed: 16586527
Angew Chem Int Ed Engl. 2021 Sep 27;60(40):21789-21794
pubmed: 34268844
Curr Protein Pept Sci. 2004 Oct;5(5):341-349
pubmed: 15551519
J Am Chem Soc. 2021 Nov 10;143(44):18481-18489
pubmed: 34723512
J Med Chem. 2016 Aug 11;59(15):7287-92
pubmed: 27434175
Angew Chem Int Ed Engl. 2004 May 3;43(19):2534-8
pubmed: 15127445
Chem Rev. 2019 Dec 26;119(24):12375-12421
pubmed: 31829013
Acc Chem Res. 2017 Jul 18;50(7):1557-1565
pubmed: 28644007
J Am Chem Soc. 2014 Feb 12;136(6):2240-3
pubmed: 24479649
Eur J Biochem. 1982 Dec;129(1):33-41
pubmed: 7160384
Biochemistry. 1994 Jan 11;33(1):200-7
pubmed: 8286341
Angew Chem Int Ed Engl. 2019 Dec 9;58(50):17986-17993
pubmed: 31609054
Biochem J. 2015 Jul 15;469(2):243-53
pubmed: 25981970
Nat Commun. 2020 Mar 27;11(1):1575
pubmed: 32221295
Nat Protoc. 2021 Mar;16(3):1740-1760
pubmed: 33597770
Biochim Biophys Acta. 2006 Jul;1760(7):1054-63
pubmed: 16635550
Angew Chem Int Ed Engl. 2016 Aug 16;55(34):9894-7
pubmed: 27304709
Curr Opin Pharmacol. 2009 Oct;9(5):608-14
pubmed: 19523876
Chemistry. 2017 Oct 17;23(58):14469-14475
pubmed: 28771849
Science. 2019 May 17;364(6441):658-664
pubmed: 31097662
Blood. 2018 Apr 26;131(17):1903-1909
pubmed: 29483100
Angew Chem Int Ed Engl. 2008;47(17):3192-5
pubmed: 18348119
Nucleic Acids Res. 2018 Jan 4;46(D1):D454-D458
pubmed: 29136213
Protein Sci. 1994 Oct;3(10):1833-9
pubmed: 7849598
Biochimie. 1990 Jun-Jul;72(6-7):431-5
pubmed: 2124146
Biochemistry. 2000 May 16;39(19):5722-30
pubmed: 10801322
Nature. 2019 May;569(7757):509-513
pubmed: 31068699
Nat Chem Biol. 2020 May;16(5):513-519
pubmed: 31907374