CN101235079A - Short peptide for inhibiting growing of liver cancer cell and application thereof - Google Patents
Short peptide for inhibiting growing of liver cancer cell and application thereof Download PDFInfo
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- CN101235079A CN101235079A CNA2008100706993A CN200810070699A CN101235079A CN 101235079 A CN101235079 A CN 101235079A CN A2008100706993 A CNA2008100706993 A CN A2008100706993A CN 200810070699 A CN200810070699 A CN 200810070699A CN 101235079 A CN101235079 A CN 101235079A
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Abstract
The invention provides a short peptide series which can inhibit the growth of hepatoma cell and an relative application, wherein the amino acid main series of the short peptide, analogue, derivative and modification have the resemblance of at least 70% and similarity of at least 90% with the amino acid main series of the short peptide, the short peptide, nucleic acid, short peptide section, short peptide analogue, short peptide derivative and short pepetide modification can be used to prepare the drug for treating the liver cancer with hepatoma cell increment, diagnosing and detecting liver caner occur and liver caner grade. The invention can resolve the defect of prior liver cancer drug which will damage normal cells as well as inhibit or kill hepatoma cell.
Description
Technical field
The invention belongs to the biotechnology field of medicaments, the present invention has more specifically related to a kind of short peptide series and application thereof that suppresses liver cancer cell growth.
Background technology
In the process of cancer generation and treatment, chemotherapy one is directly subordinate to main part.The chemotherapeutics of existing clinical use, as endoxan, cis-platinum, cytosine arabinoside, adriamycin and vincristine etc., they mainly are the cycles that is used for destroying cell, RNA, DNA and protein all are the target targets of this type of medicine.These chemotherapeutics, itself all has the toxicity of oneself, no matter be that a kind of chemotherapeutics uses separately or several chemotherapeutics is in conjunction with being used on the clinical treatment, it is having obvious curative effects to cancer, when killing and wounding kill cancer cell, also can damage patient's normal cell.The side effect of chemotherapeutics is the most general is exactly that marrow to patient produces extremely and suppresses, and causes patient's very big misery, even causes death.Up till now, except early finding the cancer state of an illness and carrying out the ocal resection enclosed mass, still there is not specific medicament to remove treatment [Cancer Biology cancer biology for the tumour that has spread, R.J.B gold work, Liu Yixun master translates, Science Press, 2002], the existing medicine that is used for cancer therapy clinically mostly is a compound, and the application of small peptide in the direct treatment aspect the cancer still do not have bibliographical information.
Summary of the invention
The present invention seeks at the problems referred to above, a kind of short peptide series and application thereof that suppresses liver cancer cell growth is provided.
A kind of small peptide that suppresses liver cancer cell growth of the present invention is characterized in that: amino acid chief series＜1 of forming small peptide〉and Nucleotide chief series＜2 of the small peptide of encoding as follows:
＜1〉J-Val-B-Trp-O-Arg wherein, J represented amino acid Pro, Asn or His; B represented amino acid Ser or Gln; O represented amino acid Leu or Thr;
＜2〉CAQ GTT or GTC or GTA or GTG GAM TGG CTN CGT or CGC or CGG or CGA wherein,
H represents Nucleotide G, A or C; Q represents Nucleotide G, T or C; M represents Nucleotide A or G; N represents Nucleotide C, A, G or T;
The amino acid main sequence of described small peptide is classified amino acid position fixed chief series as, and its choice of location is at interval arranged corresponding amino acid.
The small peptide fragment of inhibition liver cancer cell growth of the present invention, its amino acid chief series has the homogeny with this small peptide amino acid chief series 〉=70%, 〉=90% similarity, fragment have same bioactive small peptide for what described 6 amino acid whose sequences are intercepted into 3 or 4 or 5 amino acid compositions from the optional position with described small peptide.
The small peptide analogue of inhibition liver cancer cell growth of the present invention has the biological activity identical with described small peptide, and described analogue is meant at the peptide sequence or the protein that merge or form with the other polypeptide of the aminoacid sequence fusion of described small peptide or protein biologically active with described small peptide and another kind of compound.
The small peptide derivative of inhibition liver cancer cell growth of the present invention, its aminoacid sequence has the homogeny with small peptide amino acid chief series 〉=70%, 〉=90% similarity, this derivative are meant that amino acid whose one or several amino acid whose certain groups in the described amino acid whose sequence are replaced the back with other group has same bioactive small peptide with described small peptide.
The small peptide variant of inhibition liver cancer cell growth of the present invention, its aminoacid sequence has the homogeny with small peptide amino acid chief series 〉=70%, 〉=90% similarity, this variant is meant a kind of nucleotide sequence that has the aminoacid sequence of one or several amino acid or Nucleotide change or encode it, described change is included in aminoacid sequence or the nucleotide sequence, at the arbitrary topagnosis of sequence intermediary, insertion or replacement amino acid or Nucleotide, or at sequence two ends interpolation amino acid or Nucleotide.
Small peptide of the present invention, Nucleotide, small peptide fragment, small peptide analogue, small peptide derivative and small peptide variant are used to prepare all cancers, the diagnosis of the liver cancer cell infinite multiplication initiation with treatment people noumenal tumour cancer cell multiplication and detect the generation of cancer and the application of the grade malignancy medicine that cancer takes place.
Small peptide of the present invention or Nucleotide are used to prepare and have as the medicine of proteinase inhibitor or promotor or affinity reagent or the application of detection reagent.
Remarkable advantage of the present invention is: small peptide of the present invention comes from the method for using information biology the albumen of international Protein Data Bank is carried out sequence alignment, a kind of novel biologically active peptides that screens with active function, when using small peptide inhibition of the present invention or killing and wounding cancer cells normal cell is not had remarkable injury effect, solved existing cancer drug also has grievous injury to the human normal cell in inhibition or kill cancer cell defective.
Embodiment
The preparation method of small peptide adopts the method for chemosynthesis, and very sophisticated solid-phase peptide synthetic method promptly well known in the art both can adopt the Boc method also can adopt the Fmoc method.Specific practice is coupled to the inertia solid phase carrier one by one with protected amino acid exactly and gets on, and utilizes strong acid that peptide chain cracking from the carrier is got off then, removes side chain protected simultaneously.
The amino acid main sequence of small peptide is classified amino acid position fixed chief series as, its choice of location is at interval arranged corresponding amino acid, for example, amino acid in the J position has 3 kinds of Pro, Asn or His, this 3 seed amino acid can be placed in singlely＜1 on the position of J, no matter select wherein any, this small peptide still has its original biological activity, promptly suppresses the malignancy hepatic tumor cell enlargement, and similarly the amino acid of the position of B and O representative also has characteristic like this.
Nucleotide adopts the artificial synthesis preparation; The Nucleotide of coding small peptide comprises a kind of in the following group:
(a) coding has the small peptide of described aminoacid sequence or the Nucleotide of its fragment, analogue, derivative or its variant;
(b) with (a) described Nucleotide complementary Nucleotide;
(c) with (a) or Nucleotide (b) have 〉=Nucleotide of 75% homogeny;
This Nucleotide substantially by coding have＜Nucleotide of 1〉aminoacid sequence small peptide forms, nucleotide sequence of the present invention comprises＜2 in nucleotide sequence, its form is the DNA that dna form comprises cDNA or synthetic.DNA can be strand also can be double-stranded.The coding region sequence of coding small peptide can be with＜2〉in Nucleotide identical, also can be different, be called varient, wherein varient be meant and has coding＜1〉in the coding of aminoacid sequence, but can be with＜2 in Nucleotide different.Varient can be that one or several Nucleotide replaces, inserts, the nucleotide sequence of disappearance, but can not change coding＜1〉active function of the small peptide of middle aminoacid sequence.
" variant " of this small peptide or Nucleotide is meant a kind of nucleotide sequence that has the aminoacid sequence of one or several amino acid or Nucleotide change or encode it.Change can comprise disappearance, insertion, interpolation or the replacement of amino acid in aminoacid sequence or the nucleotide sequence or Nucleotide.Variant can have " conservative property " and change, and wherein the amino acid of Ti Huaning has structure or the chemical property similar with original acid, also can have " non-conservation " to change, and wherein the amino acid of Ti Huaning does not have structure or the chemical property similar with original acid." disappearance " is meant the disappearance of in aminoacid sequence or nucleotide sequence one or several amino acid or Nucleotide; " insertion " is meant in the middle optional position of aminoacid sequence or nucleotide sequence and inserts one or several amino acid; N end or C end that " interpolation " is meant at aminoacid sequence or nucleotide sequence add one or several amino acid; " replacement " is meant with different amino acid or Nucleotide and replaces one or several amino acid or Nucleotide.
This small peptide, Nucleotide, small peptide fragment, small peptide analogue, small peptide derivative and small peptide variant are used to prepare have and suppress and the purposes for the treatment of the medicine that includes but not limited to following disease:
1. noumenal tumour cancer: the Cancerous disease of liver cancer and other malignant cell propagation type.
When the amino acid chief series that calculates small peptide fragment, small peptide derivative and small peptide variant had with the homogeny of small peptide amino acid chief series and similarity, " homogeny percentage " was meant the identical percentage of sequence during two or more amino acid or nucleotide sequence are relatively.According to Cluster method (Higging D.G.﹠amp; Sharp P.M., Gene 1988,73:234-237) by checking distance between all pairings with each group series arrangement cluster, then with each bunch with in pairs or become set of dispense.Homogeny percentage between two aminoacid sequences such as sequence A and the sequence B calculates by following formula:
After " similarity " was meant that the same acid sequence position is determined in determining two aminoacid sequence comparisons, the amino acid whose conservative property of the correspondence of arranging between same amino acid replaced degree.Amino acid score PAM250 scoring matrix (Dayhoff, M.Schwartz, R.M.and Orcutt, B.C.Atlas of Protein Structure1978, the 345-352 known according to the biology information technology field; DeLisi, C.and Kanehisa, M.Mathematical Biosciences 1984.69:77-85; Schwartz, R.M.and Dayhoff, M.O.Atlas of Protein Structure, 1979.353-358), and when corresponding different aminoacids relatively during score 〉=0, these two amino acid similarities; When different aminoacids score＜0, two amino acid dissmilarities.Similarity percentage between two aminoacid sequences such as sequence C and the sequence D calculates by following formula:
Wherein, in the sequence C at interval residue number and the sequence D at interval residue number do not comprise similar amino acid whose number.
Below in conjunction with embodiment, further set forth the present invention.These implementation examples only are used to the present invention is described and are not used in and limit the scope of the invention.Following all enumerate all related synthetic small peptides of embodiment and all have the pharmic function that the present invention relates to and be not limited to cited function.
Embodiment 1
Test (the synthetic small peptide that the present invention relates to: Pro-Val-Ser-Trp-Leu-Arg) that suppresses liver cancer cell
The cultivation of Bel7402 Hepg2 cell is to cultivate with RPMI 1640 substratum that contain 10% new-born calf serum, with 5 * 10
5The cell density kind in/hole is implanted 96 porocyte plates, after 24 hours, the small peptide that the present invention relates to is joined in the Tissue Culture Plate according to different concentration, with isopyknic PBS is control group, 24, check the viable cell surviving rate with the MTT method after 48,72 hours, administration group and control group compare, and the inhibiting rate that obtains liver cancer cell can reach 71%.
Embodiment 2
Test (the synthetic small peptide that the present invention relates to: Pro-Val-Serp-Trp-Leu-Arg) that suppresses liver cancer cell
The cultivation of Bel7402 Bel-7402 cell is to cultivate with RPMI 1640 substratum that contain 10% new-born calf serum, with 5 * 10
5The cell density kind in/hole is implanted 96 porocyte plates, after 24 hours, the small peptide that the present invention relates to is joined in the Tissue Culture Plate according to different concentration, with isopyknic PBS is control group, 24, check the viable cell surviving rate with the MTT method after 48,72 hours, administration group and control group compare, and the inhibiting rate that obtains liver cancer cell can reach 75%.
Nucleotide or aminoacid sequence table
Claims (10)
1. small peptide that suppresses liver cancer cell growth is characterized in that: amino acid chief series＜1 of forming small peptide〉and Nucleotide chief series＜2 of the small peptide of encoding as follows:
＜1〉J-Val-B-Trp-O-Arg wherein, J represented amino acid Pro, Asn or His; B represented amino acid Ser or Gln; O represented amino acid Leu or Thr;
＜2〉CAQ GTT or GTC or GTA or GTG GAM TGG CTN CGT or CGC or CGG or CGA wherein,
H represents Nucleotide G, A or C; Q represents Nucleotide G, T or C; M represents Nucleotide A or G; N represents Nucleotide C, A, G or T;
The amino acid main sequence of described small peptide is classified amino acid position fixed chief series as, and its choice of location is at interval arranged corresponding amino acid.
2. the small peptide fragment of an inhibition liver cancer cell growth as claimed in claim 1, it is characterized in that: the segmental amino acid chief series of small peptide has the homogeny with described small peptide amino acid chief series 〉=70%, 〉=90% similarity, described fragment have same bioactive small peptide for what described 6 amino acid whose sequences are intercepted into 3 or 4 or 5 amino acid compositions from the optional position with described small peptide.
3. the small peptide analogue of an inhibition liver cancer cell growth as claimed in claim 1, it is characterized in that: described small peptide analogue has the biological activity identical with described small peptide, and described analogue is meant at the peptide sequence or the protein that merge or form with the other polypeptide of the aminoacid sequence fusion of described small peptide or protein biologically active with described small peptide and another kind of compound.
4. the small peptide derivative of an inhibition liver cancer cell growth as claimed in claim 1, it is characterized in that: the amino acid chief series of described small peptide derivative has the homogeny with described small peptide amino acid chief series 〉=70%, 〉=90% similarity, described derivative are meant that amino acid whose one or several amino acid whose certain groups in the described amino acid whose sequence are replaced the back with other group has same bioactive small peptide with described small peptide.
5. the small peptide variant of an inhibition liver cancer cell growth as claimed in claim 1, it is characterized in that: the amino acid chief series of described small peptide variant has the homogeny with described small peptide amino acid chief series 〉=70%, 〉=90% similarity, described variant is meant a kind of nucleotide sequence that has the aminoacid sequence of one or several amino acid or Nucleotide change or encode it, described change is included in aminoacid sequence or the nucleotide sequence, at the arbitrary topagnosis of sequence intermediary, insert or replace amino acid or Nucleotide, or add amino acid or Nucleotide at the sequence two ends.
6. according to claim 1,2,3,4 or 5 described a kind of small peptides that suppress liver cancer cell growth, it is characterized in that: the Nucleotide of described coding small peptide comprises a kind of in the following group:
(a) coding has the small peptide of described aminoacid sequence or the Nucleotide of its fragment, analogue, derivative or its variant;
(b) with (a) described Nucleotide complementary Nucleotide;
(c) with (a) or Nucleotide (b) have 〉=Nucleotide of 75% homogeny;
Described nucleosides artificial synthesis preparation.
7. the small peptide of inhibition liver cancer cell growth according to claim 6 is characterized in that: described small peptide adopts the chemical synthesis process preparation; Described Nucleotide adopts the artificial synthesis preparation.
8. application as the small peptide of claim 1,2,3,4 or 5 described inhibition liver cancer cell growths is characterized in that:
Described small peptide, Nucleotide, small peptide fragment, small peptide analogue, small peptide derivative and small peptide variant are used to prepare cancer, the diagnosis with the initiation of treatment noumenal tumour people liver cancer cell infinite multiplication and detect the generation of hepatic cancer and the application of the grade malignancy medicine that cancer takes place.
9. the application of the small peptide of an inhibition liver cancer cell growth as claimed in claim 6 is characterized in that: described Nucleotide is used to prepare liver cancer cancer, the diagnosis with treatment people noumenal tumour cancer cell multiplication and detects the generation of hepatic cancer and the application of the grade malignancy medicine that cancer takes place.
10. the application of the small peptide of an inhibition liver cancer cell growth as claimed in claim 6 is characterized in that: described small peptide or Nucleotide are used to prepare and have as the medicine of proteinase inhibitor or promotor or affinity reagent or the application of detection reagent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008100706993A CN101235079A (en) | 2008-03-04 | 2008-03-04 | Short peptide for inhibiting growing of liver cancer cell and application thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CNA2008100706993A CN101235079A (en) | 2008-03-04 | 2008-03-04 | Short peptide for inhibiting growing of liver cancer cell and application thereof |
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| CN101235079A true CN101235079A (en) | 2008-08-06 |
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| CNA2008100706993A Pending CN101235079A (en) | 2008-03-04 | 2008-03-04 | Short peptide for inhibiting growing of liver cancer cell and application thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102971336A (en) * | 2010-05-27 | 2013-03-13 | 埃斯泰·苏济·阿莱特·费卢 | Peptide for use as a medicament, in particular for the treatment of cancer |
-
2008
- 2008-03-04 CN CNA2008100706993A patent/CN101235079A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102971336A (en) * | 2010-05-27 | 2013-03-13 | 埃斯泰·苏济·阿莱特·费卢 | Peptide for use as a medicament, in particular for the treatment of cancer |
| CN102971336B (en) * | 2010-05-27 | 2015-11-25 | 埃斯泰·苏济·阿莱特·费卢 | As medicine, peptide especially for Therapeutic cancer |
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Open date: 20080806 |