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1. (WO2010071983) MUTATED VOLTAGE-GATED SODIUM CHANNEL NAV ALPHA SUBUNIT FOR IDENTIFICATION OF MODULATORS
Latest bibliographic data on file with the International Bureau

Pub. No.: WO/2010/071983 International Application No.: PCT/CA2009/001838
Publication Date: 01.07.2010 International Filing Date: 21.12.2009
IPC:
C07K 14/705 (2006.01) ,C07K 14/47 (2006.01) ,C12N 15/12 (2006.01) ,C12Q 1/02 (2006.01) ,G01N 33/567 (2006.01) ,G01N 21/64 (2006.01)
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
K
PEPTIDES
14
Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
435
from animals; from humans
705
Receptors; Cell surface antigens; Cell surface determinants
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
K
PEPTIDES
14
Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
435
from animals; from humans
46
from vertebrates
47
from mammals
C CHEMISTRY; METALLURGY
12
BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
N
MICRO-ORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICRO-ORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
15
Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
09
Recombinant DNA-technology
11
DNA or RNA fragments; Modified forms thereof
12
Genes encoding animal proteins
C CHEMISTRY; METALLURGY
12
BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
Q
MEASURING OR TESTING PROCESSES INVOLVING ENZYMES OR MICRO-ORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
1
Measuring or testing processes involving enzymes or micro-organisms; Compositions therefor; Processes of preparing such compositions
02
involving viable micro-organisms
G PHYSICS
01
MEASURING; TESTING
N
INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
33
Investigating or analysing materials by specific methods not covered by groups G01N1/-G01N31/131
48
Biological material, e.g. blood, urine; Haemocytometers
50
Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
53
Immunoassay; Biospecific binding assay; Materials therefor
566
using specific carrier or receptor proteins as ligand binding reagent
567
utilising isolate of tissue or organ as binding agent
G PHYSICS
01
MEASURING; TESTING
N
INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
21
Investigating or analysing materials by the use of optical means, i.e. using infra-red, visible, or ultra-violet light
62
Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
63
optically excited
64
Fluorescence; Phosphorescence
Applicants:
UNIVERSITE LAVAL [CA/CA]; Cité Universitaire Québec, Québec G1K 7P4, CA (AllExceptUS)
CHAHINE, Mohamed [CA/CA]; CA (UsOnly)
Inventors:
CHAHINE, Mohamed; CA
Agent:
GOUDREAU GAGE DUBUC; 2000 McGill College Suite 2200 Montréal, Québec H3A 3H3, CA
Priority Data:
61/139,79022.12.2008US
Title (EN) MUTATED VOLTAGE-GATED SODIUM CHANNEL NAV ALPHA SUBUNIT FOR IDENTIFICATION OF MODULATORS
(FR) SOUS-UNITÉ ALPHA DE CANAL SODIQUE SENSIBLE AU VOLTAGE NAV MUTÉ POUR L'IDENTIFICATION DE MODULATEURS
Abstract:
(EN) Reagents, methods and kits for screening for compounds that modulate the activity of voltage-gated sodium channels (NaV), such as human NaV1.5/SCN5A/hH1 are described. The reagents, methods and kits are based on mutated NaV alpha subunit polyptides of SEQ ID NO:5 with mutations at positions 372, 898, 1419 and 1711 (the DEKA motif) and at positions 11485, 1486 and 1487 (the IFM motif) resulting in increased permeability for a group IIA divalent cation (Ca++) and decreased inactivation rate. The mutant polypeptide is used in a method and kit for determining whether a test compound modulates the channel activity, preferably using a chimeric polypeptide (chameleon polypeptide) comprising calmodulin, a calmodulin binding protein (M13), and two fluorescent agents.
(FR) L'invention concerne des réactifs, des procédés et des kits pour la sélection de composés qui modulent l'activité des canaux sodiques sensibles au voltage (NaV), tels que le NaV1.5/SCN5A/hH1 humain. Les réactifs, les procédés et les kits sont basés sur des polypeptides mutés de sous-unité alpha NaV de SEQ ID NO:5 avec des mutations aux positions 372, 898, 1419 et 1711 (motif DEKA) et aux positions 11485, 1486 et 1487 (motif IFM), ce qui entraîne une perméabilité accrue pour un cation divalent (Ca++) du groupe IIA et un taux d'inactivation réduit. Le polypeptide mutant est utilisé dans un procédé et un kit pour déterminer si un composé de test module l'activité du canal, en utilisant de préférence un polypeptide chimère (polypeptide caméléon) comprenant de la calmoduline, une protéine de liaison à la calmoduline (M13), et deux agents fluorescents.
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Designated States: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW
African Regional Intellectual Property Organization (ARIPO) (BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW)
Eurasian Patent Organization (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM)
European Patent Office (AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR)
African Intellectual Property Organization (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG)
Publication Language: English (EN)
Filing Language: English (EN)
Also published as:
US20120040368CA2745371