Modified Natriuretic Polypeptides Reducing Hypotension
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Solution Overview
Problem
Current natriuretic polypeptides often induce severe hypotension, limiting their effectiveness in treating cardiovascular and renal diseases without causing excessive blood pressure lowering.
Innovation Solution
Development of natriuretic polypeptides with specific amino acid sequences (e.g., SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:6, SEQ ID NO:7) that activate cGMP, enhance natriuresis, and diuresis, while minimizing hypotensive effects, by modifying the sequences of existing natriuretic peptides such as ANP and BNP.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If natriuretic polypeptides are administered to increase natriuresis and diuresis, then urine flow and sodium excretion are improved, but severe hypotension is induced
Solution Approach 1:
The patent modifies the amino acid sequence parameters of natriuretic polypeptides to change their pharmacologic profile. Specifically, modifications to the N-terminal region (such as changing residues 1-6 of ANP or residues 1-10 of urodilatin) alter the peptide's binding affinity and biological activity, reducing hypotensive effects while maintaining natriuretic and diuretic efficacy.
Solution Approach 2:
The patent applies local modifications to specific regions of the natriuretic polypeptide sequence rather than changing the entire molecule. The N-terminal region is specifically targeted for modification while the C-terminal region (residues 24-28 of ANP or residues 27-32 of urodilatin) is largely preserved, creating localized changes that selectively reduce hypotension while maintaining renal effects.
2Reliability
If natriuretic polypeptides are used to treat cardiovascular and renal diseases, then therapeutic effect is improved, but blood pressure is excessively lowered
Solution Approach 1:
The patent changes the biochemical parameters of natriuretic polypeptides through amino acid substitutions, additions, or deletions. These parameter changes result in peptides with altered pharmacokinetic and pharmacodynamic properties, specifically reduced vasodilatory activity while maintaining natriuretic and diuretic effects, thereby improving therapeutic reliability without excessive blood pressure lowering.
Solution Approach 2:
The patent creates modified copies of existing natriuretic polypeptides (ANP, BNP, urodilatin) with altered sequences. These copies retain the core therapeutic functions but have modified properties that reduce adverse hypotensive effects, allowing them to serve as improved therapeutic agents for cardiovascular and renal diseases.
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
These modified polypeptides effectively treat cardiovascular and renal conditions by increasing urine flow, sodium excretion, and renal blood flow without excessively lowering blood pressure, as demonstrated by increased plasma and urinary cGMP levels and reduced renal vascular resistance.
Implementation Method 1
activate cGMP, enhance natriuresis, and diuresis, while minimizing hypotensive effects
Data Source
AI summary
This document provides natriuretic polypeptides. For example, this document provides polypeptides having a natriuretic activity. In some cases, a polypeptide provided herein can have natriuretic activities without inducing excessive hypotension. This document also provides methods and materials for inducing natriuretic activities within a mammal.