Structural formulas based on the repetitive motifs of salivary proline rich proteins mucin and collagen designed to modulate cell and tissue growth division and differentiation

Description

1) TECHNICAL AREA OF THE INVENTION

The invention represents five structural chemical formulas of the repetitive sequences (motifs) of the salivary proline rich proteins, mucin and collagen. Peptide sequences are designed for the modulation of cell and tissue growth, division and differentiation.

2) TECHNICAL PROBLEM

Bioactive parts of the protein and gene sequences are often 5 to 15 amino acid long and repetitive peptides, separated by the larger amino acid blocks of undefined function (1-5). Computational analyses may be used for the extraction of such motifs and subsequent manipulation with the bioactive effects their protein regions (1-5). The invention represents five structural formulas for the repetitive sequences (motifs) of the salivary proline rich proteins, mucin and collagen.

3) TECHNICAL DESCRIPTION

Repetitive peptide motifs within a single protein or a protein family represent, together with their matching complementary sequences, regions that are linked to the bioactivity of the larger molecular structures (1-5).

Modern programming techniques, development of the softwares and large databases of the protein and gene structures, enabled the computer modelling of repetitive, bioactive and complementary structures of the large number of different proteins (1-5). Consequently, the extraction of short and repetitive motifs may be done on a personal computer quickly and easily (1-5). We analysed repetitive peptides of the salivary proline rich proteins, mucin and collagen (6-9) by means of the software SCAN (3-5) in order to define five structural peptide formulas (SALIVAR, SALIVAL, SALIVAN, MUCOSEPT and PROCOL α) to modulate cell and tissue growth, division and differentiation.

4) PURPOSE OF THE INVENTION

The invention consists of five peptide structural formulas from the repetitive parts of the salivary proline rich proteins, mucin and type I collagen. The aim of the invention, i.e. structural formulas, is to provide short peptide sequences that modulate cell and tissue growth, division and differentiation.

The technical invention is in the fact that the sequences that model large and/or bioactive parts of the molecules of the salivary proline rich proteins, mucin and type I collagen are extracted by means of the software SCAN, instead of the random pharmacological screening. Based on the computational analyses and database search general structural formulas (motifs) have been derived as the consensus sequences salivary proline rich proteins, mucin and collagen.

5) BRIEF DESCRIPTION OF DRAWINGS

Table 1 defines repetitive peptide sequence (motif) SALIVAR.

Table 2 defines general repetitive peptide sequence (motif) SALIVAR.

Table 3 defines repetitive peptide sequence (motif) SALIVAL.

Table 4 defines general repetitive peptide sequence (motif) SALIVAL.

Table 5 defines specific peptide sequences (motifs) SALIVAL.

Table 6 defines repetitive peptide sequence (motif) SALIVAN.

Table 7 defines repetitive peptide sequence (motif) MUCOSEPT.

Table 8 defines repetitive peptide sequence (motif) PROCOL α.

Table 9 defines general and specific peptide sequences (motifs) PROCOL α.

FIG. 1 describes the partition of the amino acids according to the molecular polarity, in the sequences of the Tables 4, 5, 8 and 9.

6) DESCRIPTION OF THE POSSIBLE APPLICATIONS OF THE INVENTION

Repetitive sequences SALIVAR, SALIVAL, SALIVAN, MUCOSEPT and PROCOL α, defined in Tables 1-9 will be used as bioactive peptides for the modulation of cell and tissue growth, division and differentiation. The purpose of defining repetitive segments SALIVAR, SALIVAL and SALIVAN of the bioactive salivary proline rich proteins (8) is to obtain quickly and accurately the formula (sequence motif) that in the satisfactory way mimics the function of larger structures. Additional bioactivity of the motifs is to be obtained by combining the sequences SALIVAR, SALIVAL and SALIVAN with the repetitive sequences of their mucin or collagen matrix (MUCOSEPT, PROCOL α).

7) INDUSTRIAL APPLICATIONS OF THE INVENTION

Bioactive sequences of the formulas (motifs) SALIVAR, SALIVAL, SALIVAN, MUCOSEPT and PROCOL α, and their combination will be applied perorally, intramuscularly and intravenously. Topical applications include ointments, creams, gels, suppositories, vaginal suppositories, eye-drops and ear-drops.

REFERENCES

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FIG. 1. Division of 20 amino acids into the two groups (polar and non-polar ones), was performed by means of the statistical clustering procedure of “partitioning around medoids”, on the standard hydropathy scale of Rose et al. (10). We used parameter f of the scale, that measures “the mean frictional area loss of the amino acid residue within the protein molecule”. The analysis was done by means of the software package S-Plus, with standard pam method (11). The values of Silhouette plot presented in the figure confirm statistically significant clustering of the 20 amino acid set into the two groups of the amino acids, a and b (11). Group a of polar amino acids consists of the N, D, E, Q, P, R, S, K, T, G and A while group b of non-polar amino acids consists of the amino acids V, L, M, W, I, F, C, H and Y.