CN102120755A - Brown adipose tissue targeted polypeptide and applications thereof - Google Patents
Brown adipose tissue targeted polypeptide and applications thereof Download PDFInfo
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- CN102120755A CN102120755A CN2010101599163A CN201010159916A CN102120755A CN 102120755 A CN102120755 A CN 102120755A CN 2010101599163 A CN2010101599163 A CN 2010101599163A CN 201010159916 A CN201010159916 A CN 201010159916A CN 102120755 A CN102120755 A CN 102120755A
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Abstract
The invention relates to the technical field of biomedicine, in particular to a brown adipose tissue targeted polypeptide and applications thereof. The polypeptide of the invention is prepared by connecting amino with the C-terminus of the polypeptide CKGGRAKDC, namely CKGGRAKDC-NH2. The polypeptide with the brown adipose tissue characteristic affinity of the invention can carry therapeutic drugs with different molecular weights to the brown adipose tissue and also have potential scientific research and clinical application values when used as the specific carrier for curing obesity and body metabolic disorder.
Description
Technical field
The present invention relates to field of biomedicine technology, relate to a kind of brown adipose tissue targeted polypeptide and application thereof particularly.
Background technology
Change along with The development in society and economy, people life style, obesity has become global epidemic disease, and then causing the incidence of obesity-related disease (type ii diabetes, hypertension, hyperlipidaemia, coronary atherosclerotic heart disease etc.) and case fatality rate also sharply to rise, this has brought heavy social burden and economical load for present Chinese society.Therefore, the research and development of novel Bariatric means seem particularly important.
Fat excessive generation and the accumulation that mainly shows as white adipose tissue, and the past The experimental results both domestic and external show that it is the factor of organism metabolic disorder generation most critical that white adipose (comprising subcutaneous/interior fat) increases.Previously viewpoint thinks that brown fat exists only in newborn infant and the infants as a kind of non-trembling property heat production organ, and brown fat disappears gradually with advancing age.And in recent years along with the PET-CT The Application of Technology, clinical study both at home and abroad all reports and still exists a spot of brown fat in the human body of finding to grow up, mainly be dispersed in be distributed on neck, the clavicle, in the chest mediastinum, zones such as thoracic vertebrae is other.And further discovering to brown fat, brown fat is not only a heat production organ, its balance to the energy metabolism of body also plays keying action, metabolism disturbance states such as obesity, hyperlipidaemia, insulin resistant can be effectively resisted in the quantity of brown fat or active enhancing, increasing brown fat effectively can increase the consumption of energy, reduce white adipose and accumulate, lose weight, improve metabolism.Therefore, brown fat becomes the novel targets for the treatment of obesity, organism metabolic disorder at present.
Yet brown fat in the intravital distribution of grownup seldom can strengthen obviously and promote that the active material of brown fat is mainly the catecholamines medicine, as norepinephrine.But as a kind of common clinical application, norepinephrine can all cause very wide influence to cardiovascular circulation system, respiratory system, Digestive tract, and the adverse consequences that might cause severe arrhythmia to take place, the patient with severe symptoms's first aid that is mainly used in circulatory failure is clinically used.The use norepinephrine of general will certainly bring the serious side effects of other important organs with the effect that strengthens brown fat, and its drawback of bringing will be far longer than and strengthen the benefit that the brown fat activity is brought.Another can strengthen the active medicine of brown fat is Triiodothyronine, yet it is same, the use Triiodothyronine of general will inevitably cause body Triiodothyronine hyperfunction artificially, thereby to each system of whole body, comprise analytic metabolism function, cardiovascular systems, Digestive tract, blood system, skeletal musculature etc., all cause very bad influence and consequence.Therefore the maximum difficult point that how to strengthen the brown fat effect just is to seek out suitable targeting vector, can transport curative material target and arrive brown adipose tissue, make medicine can only act on brown adipose tissue, but other internal organs are not impacted.Do not report the carrier of this brown adipose tissue magnetic target therapy up to now both at home and abroad as yet.
Summary of the invention
The purpose of this invention is to provide a kind of brown adipose tissue targeted polypeptide.
A further object of the present invention provides the application of above-mentioned property polypeptide as brown adipose tissue target medicine carrier.
2004, famous science magazine " Nature Medcine " report found that a polypeptide can be specifically and the endothelial cell receptor combination of white adipose tissue blood vessel, and its aminoacid sequence is CKGGRAKDC.And further research also confirm this polypeptide can with have the active material of bio-pharmacology and be connected, make drug targeting arrive white adipose tissue, bring into play pharmacological effect, thereby reach the purpose of targeted therapy.The present inventor modifies aforementioned polypeptides, and then verifies its target, has obtained brown adipose tissue targeted polypeptide of the present invention.
Brown adipose tissue targeted polypeptide according to the present invention is amino in the C-terminal connection of peptide C KGGRAKDC: CKGGRAKDC-NH
2
Brown adipose tissue targeted polypeptide of the present invention can be used for carrying the curative drug with different molecular weight size and enter brown adipose tissue.
Polypeptide with brown adipose tissue characteristic affinity of the present invention can carry the curative drug with different molecular weight size and enter in the brown adipose tissue, has potential scientific research and clinical value as the idiosyncratic carrier of treatment obesity, organism metabolic disorder.In addition, this polypeptide only contains 9 amino-acid residues, and easily synthetic, spatial position change is less relatively, is easy to polypeptide is carried out quality monitoring the use aspect.The present invention has filled up the domestic and international blank of brown adipose tissue targeting substance, not only can actively promote the scientific research progress of brown fat, and is that the direction that makes new advances is expanded in treatment fat, the metabolic disorders.
Description of drawings
Fig. 1 is that polypeptide of the present invention is at the intravital tissue affinity result of C57BL/6J mouse (100 * figure).
Embodiment
Embodiment 1
The C57BL/6J male mice in age around getting, the polypeptide 10ul (strength of solution is 1mM) of mark green fluorescence FITC is gone in the mouse body by mouse tail vein injection, disconnected neck is put to death mouse behind the 10min, get flesh tissue (white adipose tissue, brown adipose tissue, muscle tissue, liver organization), lucifuge paraffin embedding immediately, section, direct viewing fluorescence under laser confocal microscope, the result only shows that in the capillary network of brown fat the green fluorescence of FITC mark expresses the most obviously, points out this polypeptide can be targeted to brown adipose tissue (result as shown in Figure 1) really.
Sequence table
＜110〉Jiangsu Prov. People's Hospital
＜120〉a kind of brown adipose tissue targeted polypeptide and application thereof
<160>1
<210>1
<211>9
<212>PRT
＜213〉artificial synthesized sequence
<400>1
CKGGRAKDC 9
Claims (2)
1. a brown adipose tissue targeted polypeptide is characterized in that, and is amino in the C-terminal connection of peptide C KGGRAKDC: CKGGRAKDC-NH
2
According to claim 1 polypeptide as the application of brown adipose tissue target medicine carrier.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN2010101599163A CN102120755B (en) | 2010-04-23 | 2010-04-23 | Brown adipose tissue targeted polypeptide and applications thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CN2010101599163A CN102120755B (en) | 2010-04-23 | 2010-04-23 | Brown adipose tissue targeted polypeptide and applications thereof |
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| Publication Number | Publication Date |
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| CN102120755A true CN102120755A (en) | 2011-07-13 |
| CN102120755B CN102120755B (en) | 2013-04-03 |
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| CN2010101599163A Expired - Fee Related CN102120755B (en) | 2010-04-23 | 2010-04-23 | Brown adipose tissue targeted polypeptide and applications thereof |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103703140A (en) * | 2011-03-30 | 2014-04-02 | 德克萨斯大学系统董事会 | Methods and compositions for targeting adipose cells in mammals |
| CN108721633A (en) * | 2018-06-06 | 2018-11-02 | 南京医科大学 | A kind of polypeptide nano bubble and its preparation method and application |
| CN111388452A (en) * | 2020-04-30 | 2020-07-10 | 中国药科大学 | Adipose tissue targeting peptide P3-chitosan oligomeric lactic acid-polyethylene glycol delivery system and application thereof in nucleic acid drug delivery |
| US10925974B2 (en) | 2018-06-06 | 2021-02-23 | Affiliated Stomatological Hospital Of Nanjing Medical University | Adipose tissue-targeting polypeptide-verbascoside-nanogold particle derivative, preparation method and application thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004020999A1 (en) * | 2002-08-30 | 2004-03-11 | Board Of Regents, The University Of Texas System | Compositions and methods of use of targeting peptides for diagnosis and therapy of human cancer |
| CN101511861A (en) * | 2006-07-21 | 2009-08-19 | 克里斯泰利亚化学药物产品有限公司 | Anti-inflammatory and antiallergic cyclic peptides |
| CN101678088A (en) * | 2007-02-14 | 2010-03-24 | 友莱尔皮肤产品有限责任公司 | Modified mutant collagenase and it's use in fat melting and in scar reduction |
| CN101678063A (en) * | 2007-01-19 | 2010-03-24 | 凯制药公司 | Methods of use of epsilon inhibitor compounds for the attenuation of pain |
-
2010
- 2010-04-23 CN CN2010101599163A patent/CN102120755B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004020999A1 (en) * | 2002-08-30 | 2004-03-11 | Board Of Regents, The University Of Texas System | Compositions and methods of use of targeting peptides for diagnosis and therapy of human cancer |
| CN101511861A (en) * | 2006-07-21 | 2009-08-19 | 克里斯泰利亚化学药物产品有限公司 | Anti-inflammatory and antiallergic cyclic peptides |
| CN101678063A (en) * | 2007-01-19 | 2010-03-24 | 凯制药公司 | Methods of use of epsilon inhibitor compounds for the attenuation of pain |
| CN101678088A (en) * | 2007-02-14 | 2010-03-24 | 友莱尔皮肤产品有限责任公司 | Modified mutant collagenase and it's use in fat melting and in scar reduction |
Non-Patent Citations (1)
| Title |
|---|
| 《Nature Medicine》 20040630 Mikhail G Kolonin, et. al， Reversal of obesity by targeted ablation of adipose tissue 第10卷, 第6期 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103703140A (en) * | 2011-03-30 | 2014-04-02 | 德克萨斯大学系统董事会 | Methods and compositions for targeting adipose cells in mammals |
| CN108721633A (en) * | 2018-06-06 | 2018-11-02 | 南京医科大学 | A kind of polypeptide nano bubble and its preparation method and application |
| US10925974B2 (en) | 2018-06-06 | 2021-02-23 | Affiliated Stomatological Hospital Of Nanjing Medical University | Adipose tissue-targeting polypeptide-verbascoside-nanogold particle derivative, preparation method and application thereof |
| CN108721633B (en) * | 2018-06-06 | 2021-06-18 | 南京医科大学 | Polypeptide nanobubble, preparation method and application thereof |
| CN111388452A (en) * | 2020-04-30 | 2020-07-10 | 中国药科大学 | Adipose tissue targeting peptide P3-chitosan oligomeric lactic acid-polyethylene glycol delivery system and application thereof in nucleic acid drug delivery |
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| Publication number | Publication date |
|---|---|
| CN102120755B (en) | 2013-04-03 |
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