Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1996-08-08
1998-03-24
Tsang, Cecilia J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
514 15, 514 16, 514 17, 514 18, 530327, 530328, 530329, 530330, 530333, A61K 3804, A61K 3808, C07K 700
Patent
active
057312893
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/GB94/02621 filed Nov. 30, 1994.
1. FIELD OF THE INVENTION
The present invention relates to the use of peptides having a stimulating effect on cell proliferation, and to novel peptides having specific and/or general cell stimulating effects.
2. DESCRIPTION OF RELATED ART
The mammalian body contains cells having enormously diverse structures and functions, and the mechanisms of differentiation and development have been the focus of much study. It is known that for systems of cells having a continuous turnover the mechanism commonly involves a reservoir of pluripotent stem cells which divide and constantly supply new cells to the system. While initially homogeneous the stem cells supplied from the "reservoir" soon become committed to one or other morphology and subsequently develop into the required functional cells:
Examples of such stem cell systems are the haemopoietic system in bone marrow and the epithelial and epidermal systems.
The manipulation or control of stem cell division is of great potential therapeutically and much research continues to be devoted to elucidating the mechanisms involved and the chemical messengers responsible. To date several biomolecules have been identified as possessing a role in cell production and differentiation either by the stimulation or inhibition of a step within the process. Myelopoiesis has been particularly well studied in this regard and molecules involved in its control include: colony-stimulating factors (CSF) such as granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), multi-lineage al J. Immunol 131: 1300 (1983)!, tumour necosis factors (.alpha. and (1989)!.
It has also been found that the haemoregulatory pentapeptide (pEEDCK) Paukovits et al Z. Naturforsch 37: 1297 (1982)! and other peptides corresponding to a narrow general formula were discovered to exert a Oxidation of the peptide monomers resulted in dimeric molecules linked by a cysteine bridge and these dimeric molecules were found to stimulate (pEEDCK).sub.2 dimer and other similar compounds are disclosed in WO-A-88/03535. Further dimeric peptide compounds are disclosed in EP-A-408371 in which the disulphide bond has been replaced by a carbon or carbon/sulphur bridge linking the selected peptide chains. The bridge is thus relatively stable to hydrolysis but is itself inert and incapable of participating in receptor-dimer interactions.
Novel single-chain peptide compounds capable of inhibiting cell proliferation are also described and claimed in our PCT application filed under No. PCT/GB93/01172 and further dimeric compounds having a stimulatory effect on cell proliferation are disclosed in our PCT applications filed as PCT/GB93/01170 and PCT/GB93/01171.
Whilst we do not wish to be bound by theoretical considerations, it is presently believed that such peptide compounds interact with stromal cells in vivo and that the stromal cells are responsible for stimulating or inhibiting cellular division via other soluble factors. The dimers are thus believed to induce or promote stromatic production of stimulatory cellular regulatory factor(s) whilst the monomeric peptides may either inhibit that process or cause the production of factors which prevent or hinder cell division. Thus, according to current thinking, the stromal cells may act to amplify the stimulatory or inhibitory effects of the dimeric and monomeric peptides respectively.
There is a continuing need for dimeric peptide compounds capable of stimulating cell proliferation to a useful level in vivo. In this regard it should be noted that different degrees of stimulation may be more appropriate to certain clinical situations than to others and, in particular, selective stimulation of individual cell types is important.
3. SUMMARY OF THE INVENTION
The present invention relates to certain novel peptides having a stimulatory effect on cell proliferation and having conformational preferences which will maximise the i
REFERENCES:
patent: 4528190 (1985-07-01), Vale, Jr. et al.
Spatola, "Chemistry and Biochemistry of Amino Acids, Peptides & Proteins" vol. 7 (Marcel Dekker 1983) pp. 284-295.
Lange Meinolf
Sandosham Jessie
Undheim Kjell
Celsa Bennett
Nycomed Imaging AS
Tsang Cecilia J.
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