REAGENT or RESOURCE | SOURCE | IDENTIFIER |
---|---|---|
Chemicals, peptides, and recombinant proteins | ||
1-Ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) | TCI | Cat# D4029 |
Carbonyldiimidazole | Sigma-Aldrich | Cat# 115533 |
3-(1H-Indazol-1-yl)-2-methylpropanoic acid | Enamine | Cat# EN300–206691 |
6-Fluoro-1H-indazol-3-amine | Enamine | Cat# EN300–100294 |
3-(3-Isopropyl-1,2,4-oxadiazol-5-yl)propanoic acid | Enamine | Cat# EN300–27664 |
4-(1-Methyl-1H-pyrazol-4-yl)pyrimidin-2-amine | Enamine | Cat# EN300–187048 |
1-(2,6-Difluorophenyl)-1H-pyrazole-3-carboxylic acid | Enamine | Cat# EN300–91144 |
3-(Methylamino)benzonitrile | Enamine | Cat# EN300–55410 |
(R,S)-7-Methyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylic acid | Enamine | Cat# EN300–309016 |
(R,S)-tert-Butyl (5-amino-5,6,7,8-tetrahydronaphthalen-2-yl)carbamate | Enamine | Cat# EN300–142125 |
3-Methoxy-2-naphthoic acid | Enamine | Cat# EN300–00001 |
3-(3-Amino-1H-pyrazol-1-yl)propanamide | Enamine | Cat# EN300–80390 |
Salicylic acid | Enamine | Cat# EN300–16723 |
2-(Chloromethyl)-5-(4-chlorophenyl)-1,3,4-oxadiazole | Enamine | Cat# EN300–08138 |
5-Amino-4-isopropyl-4H-1,2,4-triazole-3-thiol | Enamine | Cat# EN300–2493721 |
6-Chloro-2-(chloromethyl)imidazo[1,2-a]pyridine | Enamine | Cat# EN300–33589 |
5-(Benzo[d]thiazol-2-yl)thiophene-2-carboxylic acid | Enamine | Cat# EN300–00707 |
(4H-1,2,4-Triazol-3-yl)methanamine | Enamine | Cat# EN300–1264530 |
2-(Imidazo[1,2-a]pyridin-2-yl)acetonitrile | Enamine | Cat# EN300–25598 |
2-Hydroxy-2,3-dihydro-1H-indene-2-carboxylic acid | Enamine | Cat# EN300–82840 |
1-(4-Fluorophenyl)-1H-pyrazole-3-carboxylic acid | Enamine | Cat# EN300–36826 |
N-Methyl-1-(2-methylthiazol-4-yl)methanamine | Enamine | Cat# EN300–27495 |
2-Chloro-N-(3-fluoro-4-methylphenyl)propanamide | Enamine | Cat# EN300–23356 |
N4,N4-Dimethylpyrimidine-4,6-diamine | Enamine | Cat# EN300–187848 |
N-(3,4-Dimethylbenzyl)cyclopropanamine | Enamine | Cat# EN300–83837 |
1-(m-Tolyl)-1H-1,2,3-triazole-4-carboxylic acid | Enamine | Cat# EN300–61349 |
(2-Chloro-6-fluorophenyl)methanamine | Enamine | Cat# EN300–33074 |
2,2,2-trifluoroethyl carbonochloridate | Enamine | Cat# EN300–31105 |
Phenol | Alfa Aesar | Cat# A15760 |
Sodium hydride | Sigma Aldrich | Cat# H36490 |
(R)-3-Bromo-2-methylpropan-1-ol | Manchester Organics | Cat# H39016 |
(S)-3-Bromo-2-methylpropan-1-ol | Manchester Organics | Cat# R39644 |
2-Naphthol | Sigma Aldrich | Cat# 130109 |
3-(Trifluormethyl)phenol | SIAL | Cat# 156035 |
2,4-Di-tert-butylphenol | SIAL | Cat# 137731 |
4-Fluorophenol | Fisher Scientific | Cat# 10723671 |
4-Bromophenol | Acros Organics | Cat# 406511000 |
[1,1’-biphenyl]-4-ol | SIAL | Cat# 371297 |
Benzofuran-5-ol | BLD Pharmatech | Cat# BD102433 |
1-Hydroxy-7-azabenzotriazole (HOAt) | Sigma Aldrich | Cat# 41996 |
N-Ethyldiisopropylamine (DIPEA) | Acros Organics | Cat# 367841000 |
Isobutyryl chloride | Sigma Aldrich | Cat# 139122 |
1-Ethyl-3-(3-dimethylaminopropyl)carbodiimid-hydrochlorid (EDC x HCl) | Sigma Aldrich | Cat# 03450 |
(R,S)-2-methyl-3-phenoxypropionic acid | Enamine | Cat# EN300–42126 |
6-Fluoro-1H-indazole | Sigma Aldrich | Cat# APOH11A9C83A |
6-Fluoro-3-methyl-1H-indazole | Sigma Aldrich | Cat# C12H580D8864 |
4-Dimethylaminopyridine | Acros Organics | Cat# 148270050 |
Acetyl chloride | Sigma Aldrich | Cat# 114189 |
Iodomethan (methyl iodide) | Acros Organics | Cat# 122371000 |
3,5-Difluoro-2-pyridinecarbonitrile | TCI | Cat# C2753 |
Hydrazine hydrate | Acros Organics | Cat# 196711000 |
Benzotriazol-1-yl-oxytripyrrolidinophosphonium-hexafluorophosphat (PyBOP) | Merck | Cat# 8510090025 |
6-Methoxy-1H-indazol-3-amine | abcr | Cat# AB490142 |
Isopropoxy-1H-indazol-3-amine | A2B Chem | Cat# BE29241 |
6-(Trifluoromethyl)-1H-indazol-3-amine | abcr | Cat# AB146621 |
6-Chloro-1H-indazol-3-amine | BLD Pharmatech | Cat# BD167849 |
1H-Indazole-3,6-diamine | VWR International | Cat# 2C36909 |
3-Amino-1H-indazole-6-carboxylic acid | Sigma Aldrich | Cat# AMBH303C4559 |
2-Fluoro-4-(hydroxymethyl)benzonitrile | Activate Scientific | Cat# AS38375 |
1H-Indazole-6-carboxamide | abcr | Cat# AB527998 |
6-Amino-1H-indazole | abcr | Cat# AB136281 |
1-Fluoro-3-(prop-2-yn-1-yloxy)benzene (32) | Enamine | Cat# EN300–71767 |
(Acetonitrile)[2-biphenyl)di-tert-butylphosphine]gold(I) hexafluoroantimonate | Sigma Aldrich | Cat# 697575 |
Palladium hydroxide 20% on charcoal | Sigma Aldrich | Cat# 21,291–1 |
N-Bromosuccinimide | Acros Organics | Cat# 107451000 |
2.5 M Solution of butyllithium in hexane | Sigma Aldrich | Cat# 230707 |
2,2-Dimethylmalononitrile | Tokio Chemical Industry | Cat# D5514 |
3-Phenoxypropionic acid | Sigma Aldrich | Cat# P16001 |
(R,S)-2-(Phenoxymethyl)butanoic acid | Enamine | Cat# EN300–27146916 |
(R,S)-2-Methoxy-3-phenoxypropanoic acid | CHEM Space | Cat# CSC039927227 |
(R,S)-2-Methyl-4-phenylbutyric acid | Enamine | Cat# EN300–6496378 |
Sodium 4-phenylbutyrate | abcr | Cat# AB222448 |
2,2-didecylpropane-1,3-bis-β-D-maltopyranoside (LMNG) | Anatrace | NG310 |
Cholesteryl hemisuccinate (CHS) | Anatrace | CH210 |
Digitonin | Sigma-Aldrich | D141 |
sf-900 II SFM medium | Gibco | Cat#10902–088 |
Cellfectin II reagents | Invitrogen | Cat#10362–100 |
Freestyle 293 medium | Gibco | Cat#12338–018 |
PKA | NEB | Cat#P6000L |
ATP | Sigma-Aldrich | A2383 |
Critical commercial assays | ||
CNBR-activated sepharose beads | GE Healthcare | 17–0430–01 |
Superose 6, 10/300 GL | GE Healthcare | 17–5172–01 |
Deposited data | ||
Coordinates of the human CFTR in complex with ligand Z1834339853 | This paper | PDB: 8GLS |
Cryo-EM map of the human CFTR in complex with ligand Z1834339853 | This paper | EMDB: EMD-40207 |
Experimental models: Cell lines | ||
Sf9 | ATCC | CRL-1711 |
HEK293S GnTI− | ATCC | CRL-3022 |
CHO-K1 | ATCC | CRL-9618 |
CFBE41o- cells expressing F508del-CFTR and the fluorescent protein EYFP-H148Q/I152L/F46L | Sondo et al.52 | Gift by Luis J. Galietta |
Experimental models: Organisms/strains | ||
C57BL/6 mice | Hylasco Bio | C57BL/6Ncrl Mice |
Recombinant DNA | ||
Human CFTR cloned onto a modified pEG Bacmam vector suitable for expression in mammalian cells | This paper | N/A |
Software and algorithms | ||
Bruker TopSpin Version 4.2.0 | Bruker | https://www.bruker.com/en/products-and-solutions/mr/nmr-software/topspin.html |
ChemDraw Version 21.0.0 | Revvity Signals | https://revvitysignals.com/products/research/chemdraw |
Agilent Chemstation | Agilent | https://www.agilent.com/cs/library/usermanuals/Public/G2070-91126_Understanding.pdf |
Seriel EM | Mastronarde,74 | http://bio3d.colorado.edu/SerialEM |
MotionCor2 | Zheng et. al.75 | https://emcore.ucsf.edu/ucsf-motioncor2 |
RELION-3 | Zivanov et al.78 | http://www3.mrclmb.cam.ac.uk/relion |
RELION-2 | Kimanius et al.79 | http://www2.mrclmb.cam.ac.uk/relion |
cryoSPARC | Punjani et al.80 | https://cryosparc.com |
COOT | Emsley et al.81 | https://www2.mrclmb.cam.ac.uk/personal/pemsley/coot |
PHENIX | Adams et al.82 | https://www.phenix-online.org |
MolProbity | Chen et al.83
Davis et al.84 |
http://molprobity.biochem.duke.edu |
Chimera | Pettersen et al.85 | https://www.cgl.ucsf.edu/chimera |
Pymol | PyMOL | http://www.pymol.org |
GraphPad Prism 9 | GraphPad Software | http://www.graphpad.com |
pCLAMP9 | Molecular Devices | https://mdc.custhelp.com/euf/assets/content/pCLAMP_9.0_Manual.pdf |
DOCK 3.7 | Coleman et al.34 | https://dock.compbio.ucsf.edu/DOCK3.7/ https://blaster.docking.org/ |
ZINC15 | Sterling and Irwin,33 | http://zinc15.docking.org/ |
Reduce | Word et al., 1999 | N/A |
QNIFFT | Gallagher and Sharp, 1998; Sharp, 1995 | N/A |
Marvin | https://www.chemaxon.com | version 15.11.23.0, ChemAxon, 2015 |
Corina | https://www.mn-am.com/products/corina | v.3.6.0026, Molecular Networks GmbH |
Omega | https://www.eyesopen.com/omega | v.2.5.1.4, OpenEye Scientific Software |