SINGLE EXON GENES ENCODING FOR NOVEL BIO-ACTIVE PEPTIDES
The present invention relates to novel bio-active peptide hormone, process for the production of the same, and use of the same. The present invention identified novel bioactive peptide precursor and salts thereof which can be used as drugs, for example therapeutic polypeptides, ligands to discover relevant targets (e.g. GPCRs) or targets for drug intervention.
1 . A polypeptide comprising any of the amino acid sequences of SEQ ID NOs:108 or an amino acid sequence derived there from by deletion, substitution or insertion of at least one amino acid residue, a precursor thereof, an amide or ester thereof, or a salt thereof.
2 . The polypeptide of claim 1 consisting of the following amino acid sequence:
SEQ ID NO: 1
MYWMALRRISTLGSRWLGLSRVLLFRASKASFTFLSLRFSLSVAARRRST
DTDFLLHTLHAHGRHWPGQCSGVPSPLSSRGPGASGLRVSSVRS.
3 . The polypeptide of claim 1 consisting of the following amino acid sequence:
(SEQ ID NO: 2)
MGSGCARARLGLLSWLAASSGSEDALASSISVKLALELAEVAWSEGDEAE
GLAPWLSPLVQGRDSGEDREQLEAACLKRGSWAGAGKARELSPTAPKWLE
EAEERLTLRSIPL.
4 . The polypeptide of claim 1 consisting of the following amino acid sequence:
(SEQ ID NO: 3)
MLLAMSSISIFSSLFSFSSFCFTRCRLSICSPSSATLSACFFLRVAAVAS
CCRVASSRSLRIFWNSASLFLFISIWAEVAPLASSSLSLISSSSLARSER
CFSILALSVCSASISSSSSSMRA.
5 . The polypeptide of claim 1 consisting of the following amino acid sequence:
(SEQ ID NO: 4)
MATSWAGSAAPPASAAKSVVGTRPSRPGGPRSAWRRRRATLAAWTGPARA
ATATTTRAAARRPVAARTPARLAATSRATHARTWPMASPRASVTTCTCAF
RAARASPALSS.
6 . The polypeptide of claim 1 consisting of the following amino acid sequence:
(SEQ ID NO: 5)
MPRSAPRAAAAPARAPAAAAVACACCPNSAPDFFMVCGGHVRSLAGKRLF
SSPPRPACSGPNDLRSSGVSGGAVRPAARTRRRAQGEVEEEASCGEKGRR
TAERMGPVAAARAGLDAAWARRCEVPKVTTIPTRQPRAPARPGAPRRI.
7 . The polypeptide of claim 1 consisting of the following amino acid sequence:
(SEQ ID NO: 6)
MPKWRLAWPKQTRASSCGLSLPSISCASSCSASRNGGDRCSLRTTTTRHT
R
8 . The polypeptide of claim 1 consisting of the following amino acid sequence:
(SEQ ID NO: 7)
MSVWTFLKCRGNSSLLKNLLQVKVKAELLLLCLLVTHSLWSSTWSPPGVA
AVRSASTVPEENCSGSKLYVCVAKSMNSPSMLLDSEMTWPLSSLSKAHWR
VVLMRSDLGRSSTVIPKSEVSTALCSLGLQLNMASPSRARFPQ.
9 . The polypeptide of claim 1 consisting of the following amino acid sequence:
(SEQ ID NO: 8)
MASAAGEPFSMYLASAAAALCTPTASARKARGLRTEPLDEVLARGGPAAS
TLWCRCRLWPKASLYPGARKPCLAASGSDSSTSGGSATDTGPDLTPWKEV
DSDLSASMQLLMIWLTLSTSLAMVELSATELWLSGPGRPSSQSLRSGGSP
VRTSM.
10 . A DNA molecule comprising the nucleotide sequence of any of SEQ ID NOs:9-16 encoding the polypeptide of claim 1 comprising any of the amino acid sequences of SEQ ID NOs:1-8, its amide, its ester or a salt thereof.
11 . The DNA molecule of claim 10 consisting of the nucleotide sequence of SEQ ID NO:9 that encodes a polypeptide consisting of the amino acid sequence of SEQ ID NO: 1.
12 . The DNA molecule of claim 10 consisting of the nucleotide sequence of SEQ ID NO:10, encoding a polypeptide that consists of the amino acid sequence of SEQ ID NO:2.
13 . The DNA molecule of claim 10 consisting of the nucleotide sequence of SEQ ID NO:11, encoding a polypeptide consisting of the amino acid sequence of SEQ ID NO:3.
14 . The DNA molecule of claim 10 consisting of the nucleotide sequence of SEQ ID NO:12, encoding a polypeptide consisting of the amino acid sequence of SEQ ID NO:4.
15 . The DNA molecule of claim 10 consisting of the nucleotide sequence of SEQ ID NO:13, encoding a polypeptide consisting of the amino acid sequence of SEQ ID NO:5.
16 . The DNA molecule of claim 10 consisting of the nucleotide sequence of SEQ ID NO:14, encoding a polypeptide consisting of the amino acid sequence of SEQ ID NO:6.
17 . The DNA molecule of claim 10 consisting of the nucleotide sequence of SEQ ID NO:15, encoding a polypeptide consisting of the amino acid sequence of SEQ ID NO:7.
18 . The DNA molecule of claim 10 consisting of the nucleotide sequence of SEQ ID NO:16, encoding a polypeptide consisting of the amino acid sequence of SEQ ID NO:8.
19 . A recombinant vector comprising the DNA molecule of claim 10 .
20 . A method for manufacturing the polypeptide of claim 1 , comprising the steps of:
i. providing the amino acids;
ii. synthesizing the polypeptide with the amino acids of step i by solid phase or liquid phase synthesis
iii. extracting the polypeptide; and
iv. purifying the polypeptide
21 . A method of producing the polypeptide of claim 1 , comprising subjecting an amino terminus-constituting amino acid or peptide and a carboxyl terminus-constituting amino acid or peptide to condensation.
22 . A pharmaceutical composition comprising as the active agent the polypeptide of claim 1 , and a pharmaceutically acceptable carrier thereof.
23 . A method for changing physiological factors that increase the risk of arteriorsclerosis, inflammation or uncontrolled cell division in a subject comprising administering an effective amount of the pharmaceutical composition of claim 22 .
24 . An antibody to the polypeptide of claim 1 .
25 . A cell transformed or transfected with the recombinant vector of claim 19 .
26 . The method of claim 21 , further comprising the step of forming intramolecular disulfide bonds.
27 . A DNA molecule that encodes the polypeptide of claim 1 .
28 . An expression vector comprising the DNA molecule of 27 operatively associated with a promoter.
29 . A cell transformed or transfected with the expression vector of claim 28 .
30 . A method of expressing a polypeptide comprising any of the amino acid sequences of SEQ ID NOs:1-8, comprising culturing the cell of claim 29 in an appropriate cell culture medium under conditions that provide for expression of polypeptide by the cell.
31 . The method of claim 30 , further comprising the step of purifying the polypeptide.