Linear Peptides Inhibiting CK2 Phosphorylation
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Solution Overview
Problem
Current CK2 enzyme inhibitors, such as CIGB-300, face challenges due to chemical instability and complex synthesis processes, leading to inconsistencies and increased production costs, necessitating the development of smaller, more stable linear peptides for effective tumor treatment.
Innovation Solution
Identification and development of linear peptides with specific amino acid sequences (e.g., SEQ ID NO: 45-62) that inhibit CK2-mediated phosphorylation, which are chemically more stable and simpler to synthesize, and can be chemically conjugated with intracellular penetration peptides for enhanced therapeutic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CIGB-300 peptide is used as CK2 inhibitor, then antiproliferative activity is achieved, but chemical stability deteriorates due to methionine oxidation and disulfide bond formation
Solution Approach 1:
The patent removes the problematic methionine residue from the peptide sequence to eliminate oxidation issues and the cyclic structure with intramolecular disulfide bonds to prevent aggregation. This extraction of harmful structural elements maintains the core antiproliferative function while resolving the stability problems associated with CIGB-300.
Solution Approach 2:
The patent modifies the peptide structure by changing from a cyclic configuration to a linear configuration, and by altering amino acid residues (e.g., using N-methylated amino acids or D-amino acids), thereby changing the chemical parameters of the molecule to improve stability while preserving biological activity.
2Reliability
If CIGB-300 peptide structure is used, then CK2 inhibition is achieved, but synthesis complexity increases due to intramolecular disulfide bond formation
Solution Approach 1:
The patent eliminates the need for intramolecular disulfide bond formation by removing cysteine residues and adopting a linear peptide structure, thereby simplifying the synthesis process while maintaining the essential CK2 inhibition function.
Solution Approach 2:
The patent changes the peptide from cyclic to linear structure, fundamentally altering the synthesis requirements and reducing the number of steps needed for production, thereby lowering manufacturing complexity and cost.
3Reliability
If CIGB-300 peptide is used, then therapeutic effect is achieved, but production cost increases due to extra synthesis steps
Solution Approach 1:
The patent removes the complex cyclic structure and intramolecular disulfide bonds that require additional synthesis steps, thereby reducing production costs while preserving the therapeutic anti-tumor effect through the use of simpler linear peptide sequences.
Solution Approach 2:
By changing the peptide structure from cyclic to linear and using standard amino acid sequences, the patent simplifies the manufacturing process and reduces production costs while maintaining therapeutic efficacy.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
These linear peptides demonstrate comparable or superior antiproliferative activity to CIGB-300 in various cancer cell lines, with lower IC50 values and improved chemical stability, facilitating more efficient and cost-effective therapeutic product development.
Implementation Method 1
linear peptides that inhibit the phosphorylation event mediated by the enzyme Casein Kinase 2 (CK2), through direct interaction with the phosphoacceptor site on the substrate
Data Source
AI summary
Linear peptides that inhibit the phosphorylation mediated by the enzyme Casein Kinase 2 (CK2), which have an amino acid sequence selected from the group consisting of the sequences identified as SEQ ID NO: 45, SEQ ID NO: 49, SEQ ID NO: 50, and SEQ ID NO: 57-SEQ ID NO: 62, as well as polypeptides comprising said peptides and an intracellular penetrating peptide. A pharmaceutical composition comprising at least one of these linear peptides or polypeptides and a pharmaceutically acceptable carrier. The invention also discloses the use of said peptides or polypeptides for the manufacture of a drug, and a method of treating solid or liquid tumors where said drug is administered.