Cyclic Chemerin-9 Derivatives for Plasma Stability
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Solution Overview
Problem
Native chemerin-9 peptides suffer from low plasma stability, limiting their therapeutic potential for diseases such as cancer, diabetes, obesity, and inflammatory disorders.
Innovation Solution
Development of cyclic chemerin-9 derivatives with improved plasma stability, incorporating specific structural modifications such as 6-Carboxytetramethylrhodamine, fatty acids, and various amino acid sequences to enhance stability and potency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If native chemerin-9 peptides are used for therapeutic purposes, then they can target diseases such as cancer, diabetes, obesity, and inflammatory disorders, but they suffer from low plasma stability which limits their therapeutic potential
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of chemerin-9 through cyclic constraints and amino acid substitutions. Specifically, it introduces cyclic structures at positions 1-6, 2-7, 3-8, or 4-9 of the chemerin-9 sequence, and substitutes specific amino acids with D-isomers or unnatural amino acids to enhance plasma stability while preserving biological activity
Solution Approach 2:
The patent creates composite peptide structures by combining natural and modified amino acids within the chemerin-9 sequence. The cyclic constraints and mixed D/L amino acid compositions create composite structures that resist proteolytic degradation while maintaining receptor binding capability, thereby improving plasma stability without completely sacrificing therapeutic potential
2Stability of the object's composition
If cyclic structural modifications are introduced to improve plasma stability, then stability is enhanced, but the structural complexity increases
Solution Approach 1:
The patent applies segmentation by dividing the chemerin-9 peptide into specific segments that are cyclically constrained (positions 1-6, 2-7, 3-8, or 4-9) while leaving other portions flexible. This segmented cyclic approach provides stability where needed without completely rigidifying the entire structure, thereby balancing stability enhancement with manageable structural complexity
Solution Approach 2:
The patent introduces curvature through cyclic constraints that form ring structures within the peptide chain. These cyclic segments create three-dimensional conformations that protect against proteolytic attack while maintaining the overall flexibility needed for receptor interaction, thus improving stability without excessive structural complexity
Data Source
AI summary
The present invention relates to cyclic chemerin-9 derivatives of general formula (I) as described and defined herein, methods of preparing said peptides, and the use of said compounds for the treatment or prophylaxis of diseases, in particular cancer, diabetes, obesity and inflammatory disorders.