CN106084010A - Competitive binding Nav1.7/ KIF5b protein binding site polypeptide structure - Google Patents
Competitive binding Nav1.7/ KIF5b protein binding site polypeptide structure Download PDFInfo
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- CN106084010A CN106084010A CN201610500066.6A CN201610500066A CN106084010A CN 106084010 A CN106084010 A CN 106084010A CN 201610500066 A CN201610500066 A CN 201610500066A CN 106084010 A CN106084010 A CN 106084010A
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- Prior art keywords
- binding site
- polypeptide structure
- neuropathic pain
- competitive binding
- birth
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The present invention relates to drug world, particularly relate to competitive binding Nav1.7/KIF5b protein binding site polypeptide structure.Its sequence is one of the most any: ILVHSLFSMLIMCTILTNCIFMTM；NVEYTFTGIYTFESLIKILA；PWNWLDFVVIVFAYLTEFV；ALRTFRVLRALKTISVIPGL；VMILTVFCLSVFALIGLQLFMGNL；MIFFVVVIFLGSFYLINLILAVVAMA.Peptide sequence through modifying can be with competitive binding Nav1.7/KIF5b protein binding site, the minimizing Na of high selectivityv1.7 by endochylema to the transhipment of after birth, thus reduce Na on DRG after birthvThe exception of 1.7 raises, and result is it would be possible to alleviate the generation of neuropathic pain.
Description
Technical field
The present invention relates to drug world, particularly relate to competitive binding Nav1.7/ KIF5b protein binding site polypeptide knot
Structure.
Background technology
Neuropathic pain (Neuropathic pain, NeP) is one of clinical common chronic pain, the most right
In the treatment of neuropathic pain mainly based on medicine, but the generation of pain can not be shielded eventually the most completely.Utilize existing
For the advanced technology of life science, by technology further investigation nerve injury rear-guards such as molecular biology and gene interference
Filamentous actin and induced pain key Na+Cause effect relation between channel protein intracellular transport and neuropathic pain three, from nerve
Cell transmitter loss angle discloses root and the possible suppression target spot that neuropathic pain produces, and with this target spot for research
Core, is built and modifies by protein function prediction, polypeptide, treated neuropathic pain.
Research finds: Na+The exception rise of passage is the basic reason that neuropathic pain occurs.Valtage-gated Na+Passage
It is a kind of transmembrane glycoprotein, is made up of a α subunit and one or more β subunit.In the 9 kinds of hypotypes having now been found that
(Nav1.1- Nav1.9) in, Na closely-related with neuropathic pain+Passage mainly includes Nav1.3、Nav1.7、Nav1.8
And Nav1.9.Research also display: NavAlthough expression change 1.8/1.9 produces with the pain sensation and there is relation, its expression is done
Disturbing can not the generation of complete incidence graph pain.And Nav1.7 albumen make Na with the substantial connection of neuropathic painv1.7 albumen
Become the research direction being hopeful most inhibition of pain.If Na can be reducedv1.7 after birth exception raise, perhaps the most permissible
Reduce generation and the development of pathologic pain.
And Na+The transhipment of channel protein, rise have close with kinesin in intracellular in combination and lasting transport
Cut relation, block crucial kinesin and perhaps can block one or more Na+The transmitter loss of channel protein, reduces after birth Na+
Channel abnormal raises, thus reduces neuronal excitability, the final generation alleviating neuropathic pain.
Unlike other sodium-ion channels, Nav1.7 pain relievings and do not affect other sensation, be not present in heart and
Central nervous system, therefore side effect risk is little, and body is for because of NavWhat 1.7 disappearances produced presses down pain effect does not has dependency, because of
This is that preferably sodium channel is intervened in analgesia.
Assume if Na can be foundvThe binding site of 1.7 and KIF5b, and with this binding site aminoacid sequence as base
Plinth external structure micromolecule polypeptide, can be with competitive binding Na through the peptide sequence modifiedv1.7/ KIF5b protein binding position
Point, the minimizing Na of high selectivityv1.7 by endochylema to the transhipment of after birth, thus reduce Na on DRG after birthvThe exception of 1.7 raises,
Result is it would be possible to alleviate the generation of neuropathic pain.
Summary of the invention
The purpose of invention: in order to provide a kind of effect more preferable competitive binding Nav1.7/ KIF5b protein binding site
Polypeptide structure, specific purposes are shown in the multiple substantial technological effects being embodied as part.
In order to reach as above purpose, the present invention adopts the following technical scheme that:
Scheme one:
Competitive binding Nav1.7/ KIF5b protein binding site polypeptide structure, it is characterised in that
Its sequence is one of the most any:
、 ILVHSLFSMLIMCTILTNCIFMTM；
、 NVEYTFTGIYTFESLIKILA；
、 PWNWLDFVVIVFAYLTEFV；
、 ALRTFRVLRALKTISVIPGL；
、 VMILTVFCLSVFALIGLQLFMGNL；
、 MIFFVVVIFLGSFYLINLILAVVAMA 。
Scheme two:
Polypeptide structure as described in scheme one reduces Nav 1.7 by endochylema purposes in the medicine of the transhipment of after birth in preparation.
Scheme three:
The polypeptide structure as described in scheme one purposes in the medicine of neuropathic pain is alleviated in preparation.
Scheme four:
A kind of medicine treating neuropathic pain, it is characterised in that this pharmaceutical pack contains peptide fragment, comprises in the active group of peptide fragment
Following activity two kinds of binding site or two or more:
、 ILVHSLFSMLIMCTILTNCIFMTM；
、 NVEYTFTGIYTFESLIKILA；
、 PWNWLDFVVIVFAYLTEFV；
、 ALRTFRVLRALKTISVIPGL；
、 VMILTVFCLSVFALIGLQLFMGNL；
、 MIFFVVVIFLGSFYLINLILAVVAMA。
Use the present invention of as above technical scheme, have the advantages that relative to prior art: through the polypeptide modified
Sequence can be with competitive binding Nav1.7/ KIF5b protein binding site, the minimizing Na of high selectivityv1.7 by endochylema to after birth
Transhipment, thus reduce Na on DRG after birthvThe exception of 1.7 raises, and result will alleviate the generation of neuropathic pain.
Detailed description of the invention
Illustrating embodiments of the invention below, embodiment is not construed as limiting the invention:
The 6 groups of competitive binding Na announcedv1.7/ KIF5b protein binding site polypeptide structure sequence is as follows:
、 ILVHSLFSMLIMCTILTNCIFMTM
、 NVEYTFTGIYTFESLIKILA
、 PWNWLDFVVIVFAYLTEFV
、 ALRTFRVLRALKTISVIPGL
、 VMILTVFCLSVFALIGLQLFMGNL
、 MIFFVVVIFLGSFYLINLILAVVAMA
Peptide sequence through modifying can be with competitive binding Nav1.7/ KIF5b protein binding site, subtracting of high selectivity
Few Nav1.7 by endochylema to the transhipment of after birth, thus reduce Na on DRG after birthvThe exception of 1.7 raises, and result is it would be possible to alleviate
The generation of neuropathic pain.
Pain threshold experimental result: machinery pain threshold and burning pain threshold value result show, uses polypeptide fragment significantly to drop
Low pain degree, improves pain threshold.
| Machinery pain threshold (gram) | Burning pain threshold value (second) | |
| Polypeptide fragment 1 | 22.9 | 39 |
| Polypeptide fragment 2 | 32.8 | 36 |
| Polypeptide fragment 3 | 30.1 | 29 |
| Polypeptide fragment 4 | 33.3 | 38 |
| Polypeptide fragment 5 | 38.6 | 33 |
| Polypeptide fragment 6 | 29.8 | 36 |
| Matched group | 5.1 | 10 |
The ultimate principle of the present invention, principal character and advantages of the present invention have more than been shown and described.Those skilled in the art
It should be recognized that the present invention is not restricted to the described embodiments, the simply explanation present invention's described in above-described embodiment and description
Principle, without departing from the spirit and scope of the present invention, the present invention also has various changes and modifications, and these change and change
Enter and both fall within claimed scope.
<110>fourth is smooth
<120>competitive binding Nav1.7/ KIF5b protein binding site polypeptide structure
<160> 6
<210> 1
<211> 24
<212> PRT
<213>artificial sequence
<400> 1
ILVHSLFSMLIMCTILTNCIFMTM
<210>2
<211>20
<212> PRT
<213>artificial sequence
<400>2
NVEYTFTGIYTFESLIKILA
<210>3
<211> 19
<212> PRT
<213>artificial sequence
<400>3
PWNWLDFVVIVFAYLTEFV
<210>4
<211>20
<212> PRT
<213>artificial sequence
<400>4
ALRTFRVLRALKTISVIPGL
<210>5
<211>24
<212> PRT
<213>artificial sequence
<400>5
VMILTVFCLSVFALIGLQLFMGNL
<210>6
<211>26
<212> PRT
<213>artificial sequence
<400>6
MIFFVVVIFLGSFYLINLILAVVAMA
Claims (4)
1. competitive binding Nav1.7/ KIF5b protein binding site polypeptide structure, it is characterised in that
Its sequence is one of the most any:
、 ILVHSLFSMLIMCTILTNCIFMTM；
、 NVEYTFTGIYTFESLIKILA；
、 PWNWLDFVVIVFAYLTEFV；
、 ALRTFRVLRALKTISVIPGL；
、 VMILTVFCLSVFALIGLQLFMGNL；
、 MIFFVVVIFLGSFYLINLILAVVAMA 。
2. polypeptide structure as claimed in claim 1 reduces Nav 1.7 by endochylema in the medicine of the transhipment of after birth in preparation
Purposes.
3. the polypeptide structure as claimed in claim 1 purposes in the medicine of neuropathic pain is alleviated in preparation.
4. the medicine treating neuropathic pain, it is characterised in that this pharmaceutical pack contains peptide fragment, wraps in the active group of peptide fragment
Containing following activity two kinds of binding site or two or more:
、 ILVHSLFSMLIMCTILTNCIFMTM；
、 NVEYTFTGIYTFESLIKILA；
、 PWNWLDFVVIVFAYLTEFV；
、 ALRTFRVLRALKTISVIPGL；
、 VMILTVFCLSVFALIGLQLFMGNL；
、 MIFFVVVIFLGSFYLINLILAVVAMA 。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610500066.6A CN106084010A (en) | 2016-06-30 | 2016-06-30 | Competitive binding Nav1.7/ KIF5b protein binding site polypeptide structure |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610500066.6A CN106084010A (en) | 2016-06-30 | 2016-06-30 | Competitive binding Nav1.7/ KIF5b protein binding site polypeptide structure |
Publications (1)
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|---|---|
| CN106084010A true CN106084010A (en) | 2016-11-09 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610500066.6A Pending CN106084010A (en) | 2016-06-30 | 2016-06-30 | Competitive binding Nav1.7/ KIF5b protein binding site polypeptide structure |
Country Status (1)
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|---|---|
| CN (1) | CN106084010A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102597002A (en) * | 2009-10-27 | 2012-07-18 | Ucb医药有限公司 | Antibodies to ion channels |
| CN102781963A (en) * | 2009-10-27 | 2012-11-14 | Ucb医药有限公司 | Function modifying Nav 1.7 antibodies |
-
2016
- 2016-06-30 CN CN201610500066.6A patent/CN106084010A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102597002A (en) * | 2009-10-27 | 2012-07-18 | Ucb医药有限公司 | Antibodies to ion channels |
| CN102781963A (en) * | 2009-10-27 | 2012-11-14 | Ucb医药有限公司 | Function modifying Nav 1.7 antibodies |
Non-Patent Citations (2)
| Title |
|---|
| LAN BAO: "Trafficking regulates the subcellular distribution of voltage‑gated sodium channels in primary sensory neurons", 《MOL PAIN》 * |
| YUAN-YUAN SU ET AL.: "KIF5B Promotes the Forward Transport and Axonal Function of the Voltage-Gated Sodium Channel Nav1.8", 《THE JOURNAL OF NEUROSCIENCE》 * |
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Application publication date: 20161109 |