Antibody fragments structurally enable a drug-discovery campaign on the cancer target Mcl-1.
Fab
Mcl-1
drug design
scFv
Journal
Acta crystallographica. Section D, Structural biology
ISSN: 2059-7983
Titre abrégé: Acta Crystallogr D Struct Biol
Pays: United States
ID NLM: 101676043
Informations de publication
Date de publication:
01 Nov 2019
01 Nov 2019
Historique:
received:
30
06
2019
accepted:
16
10
2019
entrez:
7
11
2019
pubmed:
7
11
2019
medline:
25
2
2020
Statut:
ppublish
Résumé
Apoptosis is a crucial process by which multicellular organisms control tissue growth, removal and inflammation. Disruption of the normal apoptotic function is often observed in cancer, where cell death is avoided by the overexpression of anti-apoptotic proteins of the Bcl-2 (B-cell lymphoma 2) family, including Mcl-1 (myeloid cell leukaemia 1). This makes Mcl-1 a potential target for drug therapy, through which normal apoptosis may be restored by inhibiting the protective function of Mcl-1. Here, the discovery and biophysical properties of an anti-Mcl-1 antibody fragment are described and the utility of both the scFv and Fab are demonstrated in generating an Mcl-1 crystal system amenable to iterative structure-guided drug design.
Identifiants
pubmed: 31692474
pii: S2059798319014116
doi: 10.1107/S2059798319014116
pmc: PMC6834078
doi:
Substances chimiques
Immunoglobulin Fab Fragments
0
MCL1 protein, human
0
Myeloid Cell Leukemia Sequence 1 Protein
0
Single-Chain Antibodies
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1003-1014Informations de copyright
open access.
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