GB2393725A - Methods for identifying substances interacting with pleckstrin homologydomains, and proteins containing mutated pleckstrin homology domains - Google Patents
Methods for identifying substances interacting with pleckstrin homologydomains, and proteins containing mutated pleckstrin homology domains Download PDFInfo
- Publication number
- GB2393725A GB2393725A GB0402001A GB0402001A GB2393725A GB 2393725 A GB2393725 A GB 2393725A GB 0402001 A GB0402001 A GB 0402001A GB 0402001 A GB0402001 A GB 0402001A GB 2393725 A GB2393725 A GB 2393725A
- Authority
- GB
- United Kingdom
- Prior art keywords
- compound
- pleckstrin
- domain
- tapp
- predicted
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000000034 method Methods 0.000 title abstract 5
- 102000004169 proteins and genes Human genes 0.000 title abstract 2
- 108090000623 proteins and genes Proteins 0.000 title abstract 2
- 102000010995 Pleckstrin homology domains Human genes 0.000 title 2
- 108050001185 Pleckstrin homology domains Proteins 0.000 title 2
- 239000000126 substance Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 abstract 9
- 150000003906 phosphoinositides Chemical class 0.000 abstract 4
- 238000000302 molecular modelling Methods 0.000 abstract 2
- 229920001184 polypeptide Polymers 0.000 abstract 2
- 102000004196 processed proteins & peptides Human genes 0.000 abstract 2
- 108090000765 processed proteins & peptides Proteins 0.000 abstract 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 abstract 1
- KAICRBBQCRKMPO-UHFFFAOYSA-N phosphoric acid;pyridine-3,4-diamine Chemical compound OP(O)(O)=O.NC1=CC=NC=C1N KAICRBBQCRKMPO-UHFFFAOYSA-N 0.000 abstract 1
- 229920005646 polycarboxylate Polymers 0.000 abstract 1
- 238000007423 screening assay Methods 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4702—Regulators; Modulating activity
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2299/00—Coordinates from 3D structures of peptides, e.g. proteins or enzymes
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Toxicology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
A method for selecting or designing a compound for modulating the activity of Tandem PH domain containing Protein (TAPP), the method comprising the step of using molecular modelling means to select or design a compound that is predicted to interact with the phosphoinositide binding domain of TAPP, wherein a three-dimensional structure of at least a part of the phos-. phoinoisitide binding domain of the TAPP is compared with a three-dimensional structure of a compound, and a compound that is predicted to interact with the said phosphoinositide binding domain is selected. A method of selecting of designing a compound that modulates the activity of a PH domain-containing polypeptide, the method comprising the step of using molecular modelling means to select or design a compound that is predicted to interact with a PH domain, wherein a three-dimensional structure of a polycarboxylate, for example citrate, is compared with a three-dimensional structure of a compound, and a compound that is predicted on the basis of the structure comparison to interact with the PH domain is selected. Residues of the phosphoinositide binding site of TAPP and DAPP that are involved in determining their phosphoinositide binding specificity are identified. Polypeptides mutated at these residues are useful, for example in compound screening assays.
Description
GB 2393725 A continuation (74) Agent and/or Address for Service: (58)
Field of Search by ISA:
Eric Potter Clarkson INT CL7 C07K Park View House, 58 The Ropewalk, Other: EPO-INTERNAL, BIOSIS, WPI DATA, NOTTINGHAM, NG1 5DD, United Kingdom EMBASE, SEQUENCE SEARCH
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0118611A GB0118611D0 (en) | 2001-07-31 | 2001-07-31 | Methods |
| PCT/GB2002/003262 WO2003011901A1 (en) | 2001-07-31 | 2002-07-16 | Methods for identifying substances interacting with pleckstrin homology domains, and proteins containing mutated pleckstrin homology domains |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| GB0402001D0 GB0402001D0 (en) | 2004-03-03 |
| GB2393725A true GB2393725A (en) | 2004-04-07 |
| GB2393725B GB2393725B (en) | 2005-08-31 |
Family
ID=9919508
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB0118611A Ceased GB0118611D0 (en) | 2001-07-31 | 2001-07-31 | Methods |
| GB0402001A Expired - Fee Related GB2393725B (en) | 2001-07-31 | 2002-07-16 | Methods for identifying substances interacting with pleckstrin homologydomains, and proteins containing mutated pleckstrin homology domains |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB0118611A Ceased GB0118611D0 (en) | 2001-07-31 | 2001-07-31 | Methods |
Country Status (2)
| Country | Link |
|---|---|
| GB (2) | GB0118611D0 (en) |
| WO (1) | WO2003011901A1 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040253656A1 (en) * | 2003-06-11 | 2004-12-16 | David Williams | Method for measuring inositol triphosphate |
| GB0322689D0 (en) * | 2003-09-27 | 2003-10-29 | Medical Res Council | Methods |
-
2001
- 2001-07-31 GB GB0118611A patent/GB0118611D0/en not_active Ceased
-
2002
- 2002-07-16 WO PCT/GB2002/003262 patent/WO2003011901A1/en not_active Ceased
- 2002-07-16 GB GB0402001A patent/GB2393725B/en not_active Expired - Fee Related
Non-Patent Citations (5)
| Title |
|---|
| Biochem J; Vol 351, pp 19-31 (2000). Dowler et al. "Identification of pleckstrin-homology-domain- containing proteins..." * |
| Biochem J; Vol 358, pp 287-294 (2001). Thomas et al. "Crystal structure of the phosphatidylinositol 3, 4-bisphosphate-binding domain...." * |
| Curr Opin Cell Biol; Vol 11, pp 219-225 (1999). Leevers et al. "Signalling throh phosphoinositide 3-kinases...." * |
| Mol Cell; Vol 6, pp 373-384 (2000). Ferguson et al. "Structural basis for discrimination of 3-phosphoinositides..." * |
| Mol Cell; Vol 6, pp 385-394 (2000). Lietzke et al. "Structral basis of 3-phosphoinositide recognition..." * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2003011901A1 (en) | 2003-02-13 |
| GB2393725B (en) | 2005-08-31 |
| GB0118611D0 (en) | 2001-09-19 |
| GB0402001D0 (en) | 2004-03-03 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PCNP | Patent ceased through non-payment of renewal fee |
Effective date: 20110716 |