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1. WO2020114996 - CHIMERIC PROTEIN SWITCH FOR THE OPTOGENETIC CONTROL OF AMYLOIDOGENESIS

Publication Number WO/2020/114996
Publication Date 11.06.2020
International Application No. PCT/EP2019/083384
International Filing Date 03.12.2019
IPC
C07K 14/245 2006.01
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
14Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
195from bacteria
24from Enterobacteriaceae (F), e.g. Citrobacter, Serratia, Proteus, Providencia, Morganella, Yersinia
245Escherichia (G)
C07K 14/415 2006.01
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
14Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
415from plants
G01N 33/68 2006.01
GPHYSICS
01MEASURING; TESTING
NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
33Investigating or analysing materials by specific methods not covered by groups G01N1/-G01N31/131
48Biological material, e.g. blood, urine; Haemocytometers
50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
68involving proteins, peptides or amino acids
CPC
C07K 14/245
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
14Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
195from bacteria
24from Enterobacteriaceae (F), e.g. Citrobacter, Serratia, Proteus, Providencia, Morganella, Yersinia
245Escherichia (G)
C07K 14/415
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
14Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
415from plants
C07K 2319/35
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
2319Fusion polypeptide
35containing a fusion for enhanced stability/folding during expression, e.g. fusions with chaperones or thioredoxin
C07K 2319/60
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
2319Fusion polypeptide
60containing spectroscopic/fluorescent detection, e.g. green fluorescent protein [GFP]
C07K 2319/735
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
2319Fusion polypeptide
70containing domain for protein-protein interaction
735containing a domain for self-assembly, e.g. a viral coat protein (includes phage display)
Applicants
  • CONSEJO SUPERIOR DE INVESTIGACIONES CIENTÍFICAS (CSIC) [ES]/[ES]
Inventors
  • GIRALDO SUÁREZ, Rafael
Agents
  • PONS ARIÑO, Angel
Priority Data
18382882.103.12.2018EP
Publication Language English (EN)
Filing Language English (EN)
Designated States
Title
(EN) CHIMERIC PROTEIN SWITCH FOR THE OPTOGENETIC CONTROL OF AMYLOIDOGENESIS
(FR) COMMUTATEUR PROTÉIQUE CHIMÉRIQUE POUR LE CONTRÔLE OPTOGÉNÉTIQUE DE L'AMYLOÏDOGENÈSE
Abstract
(EN)
The present invention provides an optogenetic chimeric fusion polypeptide comprising an optimized amino acid sequence of the plant phototropin domain LOV2 fused to an amino acid sequence of the bacterial amyloidogenic effector RepA-WH1. Optimized LOV2 enables navigation through the folding landscape of RepA-WH1 from solubility to its aggregation as oligomers or amyloid fibres. Thus, this polypeptide assembles as hydrogels and amyloid fibres in the darkness, while under blue light illumination forms oligomeric particles that are proteotoxic for cells, preferably bacteria. This polypeptide is therefore proposed for inducing the formation of cytotoxic amyloid oligomers in cells that are targeted for killing.
(FR)
La présente invention concerne un polypeptide de fusion chimérique optogénétique comprenant une séquence d'acides aminés optimisée du domaine LOV2 de phototropine végétale fusionnée à une séquence d'acides aminés de l'effecteur amyloïdogène bactérien RepA-WH1. Le LOV2 optimisé permet une navigation dans le paysage pliable de RepA-WH1 de la solubilité à son agrégation en tant qu'oligomères ou fibres amyloïdes. Ainsi, le polypeptide s'assemble sous forme d'hydrogels et de fibres amyloïdes dans l'obscurité, tandis que sous éclairage de lumière bleue forme des particules oligomères qui sont protéotoxiques pour des cellules, de préférence des bactéries. Le polypeptide selon l'invention peut ainsi induire la formation d'oligomères amyloïdes cytotoxiques dans des cellules ciblées pour destruction.
Also published as
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