Ex silico engineering of cystine-dense peptides yielding a potent bispecific T cell engager.
Journal
Science translational medicine
ISSN: 1946-6242
Titre abrégé: Sci Transl Med
Pays: United States
ID NLM: 101505086
Informations de publication
Date de publication:
18 05 2022
18 05 2022
Historique:
entrez:
18
5
2022
pubmed:
19
5
2022
medline:
21
5
2022
Statut:
ppublish
Résumé
Cystine-dense peptides (CDPs) are a miniprotein class that can drug difficult targets with high affinity and low immunogenicity. Tools for their design, however, are not as developed as those for small-molecule and antibody drugs. CDPs have diverse taxonomic origins, but structural characterization is lacking. Here, we adapted Iterative Threading ASSEmbly Refinement (I-TASSER) and Rosetta protein modeling software for structural prediction of 4298 CDP scaffolds and performed in silico prescreening for CDP binders to targets of interest. Mammalian display screening of a library of docking-enriched, methionine and tyrosine scanned (DEMYS) CDPs against PD-L1 yielded binders from four distinct CDP scaffolds. One was affinity-matured, and cocrystallography yielded a high-affinity (
Identifiants
pubmed: 35584229
doi: 10.1126/scitranslmed.abn0402
pmc: PMC10118748
mid: NIHMS1884741
doi:
Substances chimiques
Antibodies, Bispecific
0
B7-H1 Antigen
0
CD3 Complex
0
Cystine
48TCX9A1VT
Peptides
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
eabn0402Subventions
Organisme : NCI NIH HHS
ID : U01 CA232490
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA015704
Pays : United States
Organisme : NIH HHS
ID : S10 OD028685
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA114567
Pays : United States
Organisme : NIH HHS
ID : S10 OD020069
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA223674
Pays : United States
Références
Methods Mol Biol. 2020;2070:363-396
pubmed: 31625107
Proc Natl Acad Sci U S A. 2011 Jun 21;108(25):10174-7
pubmed: 21606332
Nat Biotechnol. 2005 Dec;23(12):1556-61
pubmed: 16299519
Neurosurgery. 2019 Oct 1;85(4):E641-E649
pubmed: 31069381
Proc Natl Acad Sci U S A. 2014 Aug 19;111(33):E3395-404
pubmed: 25092300
Am Soc Clin Oncol Educ Book. 2021 Mar;41:1-8
pubmed: 33989024
Protein Sci. 2018 Sep;27(9):1611-1623
pubmed: 30152054
J Pharmacol Exp Ther. 2013 Jan;344(1):196-206
pubmed: 23090647
Nat Biomed Eng. 2021 Nov;5(11):1261-1273
pubmed: 34725504
J Biol Chem. 2001 Oct 19;276(42):38893-8
pubmed: 11495915
Protein Eng Des Sel. 2016 Oct;29(10):457-466
pubmed: 27578889
Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):235-42
pubmed: 21460441
Protein Eng Des Sel. 2011 Jan;24(1-2):3-9
pubmed: 21068165
United European Gastroenterol J. 2013 Feb;1(1):7-20
pubmed: 24917937
MAbs. 2020 Jan-Dec;12(1):1814583
pubmed: 32892677
Nat Biotechnol. 2019 Sep;37(9):1049-1058
pubmed: 31332324
Antimicrob Agents Chemother. 2017 Jul 25;61(8):
pubmed: 28584151
Annu Rev Anal Chem (Palo Alto Calif). 2017 Jun 12;10(1):293-320
pubmed: 28375702
J Mol Biol. 1997 Jul 4;270(1):26-35
pubmed: 9231898
J Clin Immunol. 2010 May;30(3):364-72
pubmed: 20390326
PLoS One. 2014 May 13;9(5):e97438
pubmed: 24823716
Proteins. 2009 Nov 1;77(2):359-69
pubmed: 19452550
Acta Crystallogr D Biol Crystallogr. 1997 May 1;53(Pt 3):240-55
pubmed: 15299926
Nucleic Acids Res. 2007 Jul;35(Web Server issue):W375-83
pubmed: 17452350
Methods Enzymol. 2011;487:545-74
pubmed: 21187238
Structure. 2015 Dec 1;23(12):2341-2348
pubmed: 26602187
J Hematol Oncol. 2019 Sep 5;12(1):92
pubmed: 31488176
Nat Struct Mol Biol. 2018 Mar;25(3):270-278
pubmed: 29483648
Bioconjug Chem. 2017 Sep 20;28(9):2361-2371
pubmed: 28825794
Nucleic Acids Res. 2000 Jan 1;28(1):235-42
pubmed: 10592235
Methods Enzymol. 1997;276:307-26
pubmed: 27754618
Nat Methods. 2015 Jan;12(1):7-8
pubmed: 25549265
Biomark Res. 2021 May 26;9(1):38
pubmed: 34039409
J Orthop Res. 2018 Apr;36(4):1238-1247
pubmed: 28971529
Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W500-2
pubmed: 15215436
Oncotarget. 2017 Aug 3;8(35):57964-57980
pubmed: 28938530
Medicine (Baltimore). 2021 Apr 16;100(15):e25180
pubmed: 33847617
Biologics. 2019 May 01;13:33-51
pubmed: 31118560
PLoS One. 2017 Jul 19;12(7):e0180762
pubmed: 28723914
Nature. 2021 Aug;596(7873):583-589
pubmed: 34265844
Cancer Immunol Res. 2014 Apr;2(4):361-70
pubmed: 24764583
MAbs. 2012 Jul-Aug;4(4):497-508
pubmed: 22653218
Front Endocrinol (Lausanne). 2019 Jun 11;10:352
pubmed: 31244772
Pharmaceuticals (Basel). 2021 Aug 31;14(9):
pubmed: 34577584
Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15039-44
pubmed: 20696930
Neuropsychiatr Dis Treat. 2007 Feb;3(1):69-85
pubmed: 19300539
Front Immunol. 2020 Apr 24;11:501
pubmed: 32391000
Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
pubmed: 15572765
Cancer Immunol Res. 2019 Dec;7(12):2013-2024
pubmed: 31615814
Immunol Res. 2021 Dec;69(6):471-486
pubmed: 34554405
iScience. 2020 Dec 24;24(1):101960
pubmed: 33437940
J Hematol Oncol. 2015 Sep 04;8:104
pubmed: 26337639
FEBS Lett. 2010 Jun 18;584(12):2670-80
pubmed: 20388508
Nature. 2016 Oct 20;538(7625):329-335
pubmed: 27626386
Nucleic Acids Res. 2011 Nov;39(21):e143
pubmed: 21911364
J Mol Biol. 2020 Jun 26;432(14):3989-4009
pubmed: 32304700
Nat Commun. 2017 Dec 21;8(1):2244
pubmed: 29269835
MAbs. 2018 Apr;10(3):463-475
pubmed: 29359992
Cancer Immunol Res. 2014 Nov;2(11):1023-33
pubmed: 25367977
Bioinformatics. 2018 Oct 15;34(20):3461-3469
pubmed: 29718115
Nucleic Acids Res. 2005 Apr 22;33(7):2302-9
pubmed: 15849316
Proteins. 1995 Dec;23(4):566-79
pubmed: 8749853
J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674
pubmed: 19461840
Mol Cancer Ther. 2014 Jun;13(6):1549-57
pubmed: 24674885
Nat Med. 2018 Nov;24(11):1752-1761
pubmed: 30349086
Adv Drug Deliv Rev. 2008 Sep;60(12):1421-34
pubmed: 18541331
Sci Transl Med. 2020 Mar 4;12(533):
pubmed: 32132215
Sci Rep. 2014 Dec 17;4:7518
pubmed: 25515662
Trends Biochem Sci. 2020 Apr;45(4):332-346
pubmed: 32014389