Modified Apelin Peptides Proteolytic Stability
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Solution Overview
Problem
The stability of apelin peptides is limited due to proteolytic degradation by enzymes like ACE2 and NEP, leading to reduced efficacy in cardiovascular applications, such as cardiac hypertrophy and myocardial ischemic reperfusion injury.
Innovation Solution
Development of peptidomimetics with modified amino acid sequences and attachments, such as PEGylation or PALMitoylation, to enhance resistance to ACE2 and NEP degradation, thereby increasing the stability and potency of apelin peptides.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If apelin peptides are used for cardiovascular therapy, then beneficial physiological effects are achieved, but peptide stability is reduced due to proteolytic degradation
Solution Approach 1:
The patent applies parameter changes by modifying the amino acid sequence of apelin peptides through substitutions, deletions, or additions of specific residues. These sequence modifications alter the peptide's structural parameters to reduce recognition and susceptibility to proteolytic enzymes like ACE2 and NEP, thereby improving stability while preserving cardiovascular therapeutic effects
Solution Approach 2:
The patent creates composite peptide structures by combining modified apelin sequences with stabilizing amino acid motifs or conjugating to protective moieties. This composite approach integrates the bioactive apelin core with stabilizing elements that resist proteolytic degradation, achieving both therapeutic efficacy and enhanced stability
2Reliability
If apelin peptides are administered therapeutically, then cardiovascular protection is achieved, but duration of action is limited by rapid metabolism
Solution Approach 1:
The patent applies preliminary action by pre-modifying apelin peptides with stabilizing amino acid substitutions before administration. These preemptive structural modifications protect the peptide from rapid metabolic degradation in circulation, thereby extending its duration of action while maintaining cardiovascular protective effects
Solution Approach 2:
The patent modifies physical-chemical parameters of apelin peptides through amino acid sequence changes that alter metabolic stability. These parameter changes reduce the peptide's susceptibility to enzymatic breakdown, thereby prolonging its circulation half-life and duration of therapeutic action
Data Source
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AI summary
The disclosure relates to modified apelin polypeptides having increased stability against kaliikrein, NEP and ACE2 degradation and/or potency relative to the native apelin-13 and apelin-17 polypeptides. Embodiments also disclose methods of using the polypeptides for treating cardiovascular disorders.