Discovery of APL-1030, a Novel, High-Affinity Nanofitin Inhibitor of C3-Mediated Complement Activation.
affitin
alternative scaffold protein
complement
molecular biology
Journal
Biomolecules
ISSN: 2218-273X
Titre abrégé: Biomolecules
Pays: Switzerland
ID NLM: 101596414
Informations de publication
Date de publication:
11 03 2022
11 03 2022
Historique:
received:
13
12
2021
revised:
11
02
2022
accepted:
07
03
2022
entrez:
25
3
2022
pubmed:
26
3
2022
medline:
30
4
2022
Statut:
epublish
Résumé
Uncontrolled complement activation contributes to multiple immune pathologies. Although synthetic compstatin derivatives targeting C3 and C3b are robust inhibitors of complement activation, their physicochemical and molecular properties may limit access to specific organs, development of bifunctional moieties, and therapeutic applications requiring transgenic expression. Complement-targeting therapeutics containing only natural amino acids could enable multifunctional pharmacology, gene therapies, and targeted delivery for underserved diseases. A Nanofitin library of hyperthermophilic protein scaffolds was screened using ribosome display for C3/C3b-targeting clones mimicking compstatin pharmacology. APL-1030, a recombinant 64-residue Nanofitin, emerged as the lead candidate. APL-1030 is thermostable, binds C3 (K
Identifiants
pubmed: 35327625
pii: biom12030432
doi: 10.3390/biom12030432
pmc: PMC8946527
pii:
doi:
Substances chimiques
Amino Acids
0
Complement C3
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Références
Immunopharmacology. 2000 Aug;49(1-2):133-48
pubmed: 10904113
J Immunol. 2020 Jan 15;204(2):306-315
pubmed: 31907273
Bioconjug Chem. 2017 Sep 20;28(9):2361-2371
pubmed: 28825794
Semin Hematol. 2018 Jul;55(3):167-175
pubmed: 30032754
Int J Cancer. 2021 Jun 15;148(12):3019-3031
pubmed: 33506516
Cell Res. 2010 Jan;20(1):34-50
pubmed: 20010915
Mol Immunol. 2006 Mar;43(7):1010-9
pubmed: 15961157
Ophthalmology. 2020 Feb;127(2):186-195
pubmed: 31474439
Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
pubmed: 15572765
N Engl J Med. 2021 Mar 18;384(11):1028-1037
pubmed: 33730455
Proc Natl Acad Sci U S A. 2007 Nov 13;104(46):17983-8
pubmed: 17984049
Bioconjug Chem. 2017 Sep 20;28(9):2211-2223
pubmed: 28767228
J Immunol. 2014 May 15;192(10):4844-51
pubmed: 24729617
Mol Immunol. 2003 Jan;39(10):557-66
pubmed: 12431389
Nat Rev Neurol. 2020 Nov;16(11):601-617
pubmed: 33005040
Blood Rev. 2017 Jul;31(4):213-223
pubmed: 28215731
Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):235-42
pubmed: 21460441
J Immunol. 1996 Jul 15;157(2):884-91
pubmed: 8752942
Front Immunol. 2019 Jun 14;10:1157
pubmed: 31258525
Front Immunol. 2015 May 26;6:257
pubmed: 26074922
Signal Transduct Target Ther. 2021 Feb 8;6(1):53
pubmed: 33558455
Mol Immunol. 2019 Oct;114:341-352
pubmed: 31446305
Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2184-95
pubmed: 15572771
Immunotargets Ther. 2020 Dec 15;9:317-331
pubmed: 33365280
PLoS One. 2015 Nov 05;10(11):e0142304
pubmed: 26539718
Methods Mol Biol. 2012;805:315-31
pubmed: 22094814
Nat Methods. 2010 Nov;7(11):901-3
pubmed: 20935651
Front Immunol. 2015 Jun 02;6:262
pubmed: 26082779
Immunobiology. 2016 Jun;221(6):740-6
pubmed: 26101137
Mol Immunol. 2020 Dec;128:175-187
pubmed: 33137606
Sci Rep. 2020 Nov 12;10(1):19703
pubmed: 33184451
J Mol Biol. 1996 Dec 13;264(4):784-805
pubmed: 8980686
Front Immunol. 2019 Mar 04;10:362
pubmed: 30886620
Adv Exp Med Biol. 2008;632:273-92
pubmed: 19025129
Nucl Med Biol. 2017 Aug;51:33-39
pubmed: 28575696
J Biol Chem. 2009 Apr 17;284(16):10473-9
pubmed: 19196712
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):125-32
pubmed: 20124692
Acta Crystallogr D Biol Crystallogr. 2013 Jul;69(Pt 7):1204-14
pubmed: 23793146
Front Neurol. 2020 Apr 21;11:279
pubmed: 32373052
Biologics. 2008 Jun;2(2):205-22
pubmed: 19707355
J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674
pubmed: 19461840
J Biol Chem. 2007 Oct 5;282(40):29241-7
pubmed: 17684013
Nat Immunol. 2010 Sep;11(9):785-97
pubmed: 20720586
EMBO J. 2015 Nov 12;34(22):2735-57
pubmed: 26489954
Front Immunol. 2019 May 15;10:1007
pubmed: 31156618