MIC-1 Compounds with N-terminal Extensions for Metabolic Disorders
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Solution Overview
Problem
Current MIC-1 compounds face challenges with low solubility and chemical instability, limiting their therapeutic potential for treating metabolic disorders such as obesity and diabetes.
Innovation Solution
Development of MIC-1 compounds with N-terminal amino acid extensions that enhance solubility and stability, specifically by modifying the amino acid sequence and adding acidic residues to decrease the isoelectric point, thereby improving biophysical properties and receptor potency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If MIC-1 compounds are used for treating metabolic disorders, then therapeutic efficacy is improved, but solubility and chemical stability deteriorate
Solution Approach 1:
The patent modifies the isoelectric point parameter of MIC-1 compounds by adding N-terminal acidic amino acid extensions, which changes the chemical properties to improve both solubility and stability while maintaining therapeutic efficacy
Solution Approach 2:
The patent creates composite MIC-1 compounds by combining the native MIC-1 polypeptide with N-terminal acidic amino acid extensions, resulting in a composite structure that exhibits improved solubility and chemical stability while retaining biological activity
2Reliability
If MIC-1 compounds are used for treating metabolic disorders, then therapeutic efficacy is improved, but solubility deteriorates
Solution Approach 1:
The patent changes the solubility parameter by modifying the isoelectric point through addition of N-terminal acidic amino acid extensions, thereby improving aqueous solubility while maintaining therapeutic efficacy
Solution Approach 2:
The patent applies local modification by adding acidic amino acid extensions specifically at the N-terminus of the MIC-1 polypeptide, which locally alters the charge distribution and improves overall solubility without affecting the core functional regions
Data Source
AI summary
The invention relates to MIC-1 compounds. More specifically it relates to compounds comprising a MIC-1 polypeptide and an N-terminal amino acid extension, wherein said extension consists of 3 to 36 amino acid residues and where the compound has a calculated pI lower than 6.5. The compounds of the invention have MIC-1 activity. The invention also relates to pharmaceutical compositions comprising such compounds and pharmaceutically acceptable excipients, as well as the medical use of the compounds.