Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1998-07-13
2000-05-09
Davenport, Avis M.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
514 13, 514 14, 514 15, A61K 3800
Patent
active
060604484
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to growth promoters.
It has long been known that milk contains growth promoting activity for cells that is additional to its nutritional content. Thus, Epidermal Growth Factor (EGF) has been identified in human (Shing and Klagsbrun, 1984, Petrides, 1985), rat (Raaberg et al, 1990) swine (Tan et al 1990) and goat (Brown and Blakeley, 1983) milk.
Indeed the EGF present in rat milk has been shown to be significant for the normal development of pups (Oka et al 1983). EGF has not, however, been found in bovine milk (Read 1985). Instead insulin-like growth factor (IGF) I and II (Francis et al, 1986) and bovine colostrum growth factor (BCGF), which is structurally related to Platelet-derived Growth Factor (PDGF) (Shing and Klagsbrun, 1984, Brown and Blakeley, 1984), have been identified.
EP0457565 discloses milk protein hydrolyzates and compositions which are effective in the conditioning of hair and skin.
The applicant has surprisingly discovered that bovine milk contains growth promoting activity for rat mammary fibroblast cell line (Rama 27), which is not significantly stimulated by IGF or PDGF.
Furthermore, they have identified peptide sequences which elicit this growth promoting activity.
The invention relates to a peptide or a salt thereof comprising an amino acid sequence substantially identical to the C-terminal end of the .alpha.-S2 casein precursor.
According to a first aspect of the present invention there is provided the use of a peptide or a salt thereof comprising an amino acid sequence of from 9-31 amino acids in length and which is substantially identical to the C-terminal end of an .alpha.-S2 casein precursor including homologues thereof in which: another; and/or another, for the manufacture of a medicament or foodstuff for promoting growth.
Whilst whole casein protein shows no growth activity, the applicant has identified a number of peptides, derived from the C-terminal end of Bovine .alpha.-S2 casein, which elicit growth promoting activity.
Indeed, the applicant has shown this growth promoting activity to be present in at least peptides of 9 to 31 amino acids in length which have been derived from the C-terminal end of Bovine .alpha.-S2 casein. It is reasonable to hypothesise that the natural sequence responsible for the growth promoting activity is the sequence comprising the last 9 amino acids of the C-terminal end or an even shorter sequence from within the 9 amino acid sequence, possibly an 8 or 7 amino acid sequence. Indeed, it may be as short as a 3 amino acid sequence.
The bovine .alpha.-S2 casein precursor is characterised in that it has an amino acid sequence:
[CAS2.sub.-- BOVIN] ALPHA-S2 CASEIN PRECURSOR. SEQUENCE
MKFFIFTCLL AVALAKNTME HVSSSEESII SQETYKQEKN MAINPSKENL CSTFCKEVVR
(SEQ ID NO:6)
- NANEEEYSIG SSSEESAEVA TEEVKITVDD KHYQKALNEI NQFYQKFPQY LQYLYQGPIV
- LNPWDQVKRN AVPITPTLNR
EQLSTSEENS KKTVDMESTE
VFTKKTKLTE EEKNRLNFLK
- KISQRYQKFA LPQYLKTVYQ
HQKAMKPWIQ PKTKVIPYVR
YL
In three letter codes this translates to:
[CAS2 BOVIN] ALPHA-S2 CASE IN PRECURSOR. SEQUENCE
MetLysPhePheIlePheThrCysLeuLeu
(SEQ ID NO:6)
AlaValAlaLeuAlaLysAsnThrMetGlu
- HisValSerSerSerGluGluSerIleIle
SerGlnGluThrTyrLysGlnGluLysAsn
- MetAlaIleAsnProSerLysGluAsnLeu
CysSerThrPheCysLysGluValValArg
- AsnAlaAsnGluGluGluTyrSerIleGly
SerSerSerGluGluSerAlaGluValAla
- ThrGluGluValLysIleThrValAspAsp
LysHisTyrGlnLysAlaLeuAsnGluIle
- AsnGlnPheTyrGlnLysPheProGlnTyr
LeuGlnTyrLeuTyrGlnGlyProIleVal
- LeuAsnProTrpAspGlnValLysArgAsn
AlaValProIleThrProThrLeuAsnArg
- GluGlnLeuSerThrSerGluGluAsnSer
LysLysThrValAspMetGluSerThrGlu
- ValPheThrLysLysThrLysLeuThrGlu
GluGluLysAsnArgLeuAsnPheLeuLys
- LysIleSerGlnArgTyrGlnLysPheAla
LeuProGlnTyrLeuLysThrValTyrGln
- HisGlnLysAlaMetLysProTrpIleGln
ProLysThrLysValIleProTyrValArg
- TyrLeu
The applicant has found that short peptide sequences incorporating the C-terminal sequence -LysValIleProTyrValArgTyrLeu (SEQ ID NO:1) show growth promoting activity.
According t
REFERENCES:
Biochem. Soc. Trans., vol. 24, No. 3, 1996, p. 342S, Liu, Q.: "A growth factor activity in bovine milk" 658th Meeting Liverpool--Held at the University of Liverpool Apr. 16-19, 1996.
Kizawa et al., Chem Abstracts, 121:292792.
Liu Qing-Ming
Smith John Arthur
Wilkinson Mark Charles
Davenport Avis M.
Pepsyn Limited
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