Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – 15 to 23 amino acid residues in defined sequence
Patent
1995-03-10
1997-11-04
Tsang, Cecilia J.
Chemistry: natural resins or derivatives; peptides or proteins;
Peptides of 3 to 100 amino acid residues
15 to 23 amino acid residues in defined sequence
530327, 530328, A61K 3800, C07K 706, C07K 708
Patent
active
056841299
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
This invention relates generally to receptor binding domains in proteins and more specifically, to specific peptides that interact with the Type 1 human interferon receptor complex.
In order for any pharmaceutical composition to be therapeutically effective, it must be formulated in such a way that it reaches the desired target cells intact. Moreover, once at the site of action, the therapeutic must specifically interact with the target cells. Thus, the design and development of suitable carrier molecules, that may themselves be inert or active, allows for effective targeting of clinically active drugs. Much work has been done in the field of carriers for pharmaceutical compositions. Most recently, peptides have been identified as potentially suitable carriers for pharmaceutical compositions.
The interferons (hereinafter referred to as IFNs) are a family of biologically active proteins that are classified into three major groups, namely, IFN-alpha, IFN-beta and IFN-gamma. IFNs affect a wide variety of cellular functions, related to cell growth control, the regulation of immune responses and more specifically, the induction of antiviral responses. The ability of IFNs to modulate cell growth is observed with many cell types and is particularly effective in the case of tumor cells, which has led to the widespread interest in the use of IFNs for the treatment of neoplaslias.
The presence of a specific receptor at the cell surface is the first requirement for IFN action. Cells that lack these specific receptors are resistant to the effects of IFN. Receptor binding studies have identified the existence of at least two functional IFN receptors that are integral parts of the cell membrane on human cells. Branca, A. A. and Baglioni, C., (1981) Nature 294, 768-770 report that IFN-alpha and IFN-beta bind to one type of receptor and Anderson, P. et al, (1982) J. Biol. Chem. 257, 11301-11304 report that IFN-gamma binds to a separate receptor. IFN receptors are ubiquitous and more specifically, are upregulated in metabolically active cells such as cancer cells and infected tissues. Although several of the effects of IFNs such as the antiviral state, take several hours to develop, signal transduction immediately following the binding of IFN to its receptor is a rapid event. Since metabolic changes, such as increases in the transcriptional rate of some IFN-induced genes can be detected within five minutes of the addition of IFN, at least some of the transmembrane signals must be very rapid. Hannigan et al, (1986) EMBO J. 5, 1607-1613 suggest that receptor occupancy modulates the transcriptional response of specific genes to IFN. Indeed, there is accumulating evidence to suggest that there is a direct relationship between the number of receptors occupied and the amount of signal that is transduced to the cell nucleus. These transduced signals result in altered gene expression in the nucleus, which mediates the subsequent biological responses.
Extensive studies were undertaken to define those critical clusters of amino acids in the different IFN-alphas and IFN-beta that interact with the Type 1 IFN receptor complex. It is thought that these critical peptide domains would serve as prototypes for synthetic peptides that are useful as carriers for pharmaceutical compositions.
SUMMARY OF THE INVENTION
Thus, the present invention is directed to novel peptides which are carriers for pharmaceutical compositions.
More specifically, the invention is directed to novel IFN-receptor binding peptides that are designed as carriers for pharmaceutical compositions.
To this end, in one of its aspects, this invention provides a novel peptide having an amino acid sequence of CYS-LEU-LYS-ASP-ARG-HIS-ASP. (SEQ. ID NO. 1)
In another of its aspects, the invention provides a novel peptide having an amino acid sequence of ASP-GLU-SER-LEU-LEU-GLU-LYS-PHE-TYR-THR-GLU-LEU-TYR-GLN-GLN-LEU-ASN-ASP. (SEQ. ID NO. 2)
In still another of its aspects, the invention provides a novel peptide having a sequence of amino acids as f
REFERENCES:
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Marcucci, F., De Maeyer, E.; Biochem. Biophys. Res. Commun. 134: 1412-1418, 1986; p. 1417.
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Bazan, Proc. Natl. Acad. Sci., 87: 6934-6938, (1990).
Anderson, et al, J. Biol. Chem. 257, pp. 11301-11304 (1982).
Hannigan et al, EMBRO J. vol. 5, pp. 1607-1613 (1986).
Marshall S. G.
Tsang Cecilia J.
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