Peptide Inhibitor for EndoG Specificity in Leukemia Prevention
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current EndoG inhibitors are non-specific, potentially leading to chemotherapy resistance and undesirable effects on normal cells, while there is a need for targeted interference to block EndoG nuclease activity specifically.
Innovation Solution
A peptide with the amino acid sequence EX1EAX2SGSS, where X1 and X2 represent linkers or amino acid deletions, is developed to selectively inhibit EndoG nuclease activity with high specificity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If small molecule EndoG inhibitors are used to suppress nuclease activity, then cytoprotective effect is achieved, but chemotherapy resistance may occur due to nonspecific inhibition
Solution Approach 1:
The patent applies local quality by designing a peptide inhibitor that specifically targets EndoG nuclease activity through a defined amino acid sequence (EX1EAX2SGSS motif), rather than using nonspecific small molecules. This localized, sequence-specific approach allows selective inhibition of EndoG without broadly suppressing all nuclease activities, thereby maintaining chemotherapy efficacy while providing cytoprotection against therapy-induced leukemias.
2Reliability
If conventional small molecules are used for EndoG inhibition, then cytoprotective effect is achieved, but targeted interference is difficult to achieve
Solution Approach 1:
The patent applies parameter changes by transitioning from small molecule inhibitors to peptide-based inhibitors with specific amino acid sequences. This parameter change (from small molecules to peptides) enables targeted interference through sequence-specific binding to EndoG, while maintaining the cytoprotective effect. The peptide sequence parameters (specific amino acid residues and motifs) provide the necessary specificity that small molecules cannot achieve.
3Object-affected harmful factors
If EndoG nuclease activity is inhibited to prevent MLLbcr rearrangements, then secondary leukemia prevention is achieved, but cytotoxic effects of chemotherapeutic agents may be reduced
Solution Approach 1:
The patent applies the intermediary principle by using a peptide inhibitor as a mediator that specifically blocks EndoG nuclease activity without interfering with the cytotoxic mechanisms of chemotherapeutic agents. The peptide acts as an intermediary molecule that selectively binds to EndoG and prevents its DNA-cleaving activity, thereby preventing MLLbcr rearrangements and secondary leukemia, while allowing chemotherapy-induced apoptosis to proceed unaffected.
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
The peptides effectively inhibit EndoG with high specificity, reducing MLLbcr rearrangements during replication stress without affecting the cytotoxic effects of chemotherapeutic agents, thereby preventing secondary leukemias.
Implementation Method 1
peptides were found that inhibit EndoG with high specificity... the motif EX1EAX2SGSS according to SEQ ID No. 1 is relevant for binding of the peptides to EndoG and specific EndoG inhibition
Data Source
AI summary
The present invention relates to a peptide comprising an amino acid sequence EX1EAX2SGSS according to SEQ ID No. 1, or a pharmaceutically acceptable salt thereof, wherein X1 and X2 independently represent a linker which links the adjoining amino acids or an amino acid deletion, and wherein the peptide has an overall length in the range of from 7 to 30 amino acids. The present invention further relates to a pharmaceutical composition comprising the peptide, and the peptide for use in the preventive treatment of acute lymphoblastic leukemia, myelodysplastic syndrome or acute myeloid leukemia, particularly therapy-related acute lymphoblastic leukemia, therapy-related myelodysplastic syndrome or therapy-related acute myeloid leukemia.