Peptide Derivatives with Beta-Alanine Substitution for Carbonyl Quenching
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Solution Overview
Problem
Current compounds with carbonyl-quenching activity, such as dipeptide derivatives, face limitations in metabolic stability and efficacy in addressing oxidative stress-related disorders like neurodegenerative diseases and diabetes, where reactive carbonyl compounds like 4-hydroxy-trans-2-nonenal (HNE) play a significant role.
Innovation Solution
Development of peptide or pseudopeptide derivatives containing a nitrogenous heterocyclic residue with double substitution on the beta-alanine chain and a hydroxymethyl group, enhancing metabolic stability and carbonyl-quenching activity compared to L-carnosine and structurally correlated compounds.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If dipeptide derivatives with carbonyl-quenching activity are used, then carbonyl-quenching activity is improved, but metabolic stability deteriorates
Solution Approach 1:
The patent modifies the chemical structure of dipeptide derivatives by introducing specific substitutions at the beta-alanine chain (methyl groups at positions 2 and 2, or ethyl groups at position 2) and modifying the terminal carboxyl group with a hydroxymethyl group. These parameter changes in molecular structure result in compounds that maintain high carbonyl-quenching activity while achieving significantly improved metabolic stability compared to L-carnosine
Solution Approach 2:
The invention creates composite molecular structures by combining specific amino acid residues (beta-alanine with double substitution) and heterocyclic residues (histidine, tryptophan, or 5-methyltryptophan) in defined configurations. This composite approach produces derivatives that synergistically achieve both high carbonyl-quenching activity and enhanced metabolic stability
2Reliability
If L-carnosine is used as a carbonyl quencher, then carbonyl-quenching activity is achieved, but metabolic stability is insufficient
Solution Approach 1:
The patent systematically varies structural parameters of L-carnosine by introducing double substitution at the beta-alanine chain (with methyl or ethyl groups) and modifying the terminal carboxyl group. These parameter changes produce derivatives with enhanced metabolic stability while preserving or improving carbonyl-quenching activity, directly addressing the limitations of L-carnosine
Data Source
AI summary
Disclosed are peptide or pseudopeptide derivatives containing a nitrogenous heterocyclic residue with blocking activity against the by-products of lipid oxidative stress, and in particular of unsaturated aldehydes such as malondialdehyde and 4-hydroxy-trans-2-nonenal (HNE).