PTH mimetic peptide based on protein domain reconstruction and application thereof
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing osteoporosis treatments, such as teriparatide, promote both bone synthesis and resorption, leading to inconsistent therapeutic effects, and there is a need for a drug that can enhance bone synthesis while minimizing bone resorption.
Innovation Solution
A novel PTH mimetic peptide, specifically PTH (1-34) with modified 29-34 peptide fragments, including changes at the 34th position from phenylalanine to tyrosine, enhances osteoblast differentiation and bone synthesis without significantly promoting osteoclast activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Strength
If natural PTH (1-34) is used to treat osteoporosis, then bone synthesis is promoted, but bone resorption is also promoted leading to inconsistent therapeutic effects
Solution Approach 1:
The patent divides the PTH peptide into functional domains: the 1-28 region responsible for bone synthesis and the 29-34 region responsible for bone resorption. By selectively repeating and modifying the 29-34 segment, the patent creates a peptide that maintains bone synthesis while controlling bone resorption effects.
Solution Approach 2:
The patent applies local modification to the 29-34 peptide segment by changing specific amino acids (positions 34 and the last amino acid of the repeat unit from phenylalanine to tyrosine). This localized change alters the biological activity of that specific region to reduce bone resorption promotion while preserving overall bone synthesis effects.
2Productivity
If continuous large dose PTH is used, then bone resorption is promoted, but bone synthesis is inhibited
Solution Approach 1:
The patent employs intermittent administration rather than continuous dosing. The peptide is administered in periodic cycles (e.g., 5 days on, 2 days off), which allows the bone synthesis effects to accumulate while preventing the bone resorption effects from becoming dominant, thus resolving the contradiction between productivity and strength.
3Reliability
If anti-bone resorption drugs are used, then bone quality is not effectively improved, but long-term medication is required
Solution Approach 1:
The patent creates a peptide where the 29-34 segment is repeated once, creating a structure that continuously provides both bone synthesis and controlled bone resorption effects. This repeated structure ensures that the useful action (bone synthesis) is maintained without requiring long-term medication adjustment.
Data Source
AI summary
A PTH(1-34) mimetic peptide and a pharmaceutical composition for preventing or treating osteoporosis or promoting bone growth are provided. The mimetic peptide contains peptide fragment repeats at 29th-34th positions. Structure of the mimetic peptide is PTH(1-F34Y)(29-F34Y), and the amino acid sequence of the mimetic peptide is SEQ ID NO: 3. The pharmaceutical composition includes an active ingredient and a pharmaceutically acceptable carrier. The active ingredient of the pharmaceutical composition contains the PTH mimetic peptide.