Linear Natriuretic Peptide Constructs for Heart Failure
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current natriuretic peptide therapies, such as Natrecor, have limited bioavailability, short half-life, and require intravenous administration, restricting their use to hospital settings and lacking prolonged therapeutic effects for conditions like congestive heart failure.
Innovation Solution
Development of linear natriuretic peptide constructs incorporating ring-constrained amino acid surrogates and optional prosthetic groups, which enhance receptor binding affinity, stability, and bioavailability, allowing for administration routes beyond intravenous injection, such as subcutaneous or intramuscular, and providing prolonged therapeutic effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If conventional natriuretic peptide therapies are used, then therapeutic effect is achieved, but bioavailability is limited and half-life is short
Solution Approach 1:
The patent modifies the chemical structure of natriuretic peptides by incorporating ring-constrained amino acid surrogates and prosthetic groups, changing molecular parameters to achieve prolonged half-life and improved bioavailability while maintaining therapeutic activity
Solution Approach 2:
The invention creates composite peptide constructs combining conventional amino acid sequences with ring-constrained surrogates and prosthetic groups, resulting in molecules that exhibit enhanced pharmacokinetic properties including extended half-life and improved bioavailability
2Ease of operation
If intravenous administration is used, then rapid therapeutic effect is achieved, but use is restricted to hospital settings
Solution Approach 1:
By modifying the molecular structure through ring-constrained surrogates and prosthetic groups, the patent enables alternative administration routes (subcutaneous, intramuscular) beyond intravenous, allowing use in outpatient and home settings while maintaining therapeutic efficacy
3Duration of action of stationary object
If conventional natriuretic peptides are used, then acute effects are achieved, but prolonged therapeutic effects are lacking
Solution Approach 1:
The patent extends the duration of therapeutic action by incorporating ring-constrained amino acid surrogates and prosthetic groups that resist enzymatic degradation, reducing dosing frequency and enabling prolonged therapeutic effects in conditions like congestive heart failure
4Reliability
If linear peptide constructs are synthesized, then receptor binding affinity is enhanced, but structural complexity increases
Solution Approach 1:
The patent enhances receptor binding affinity by incorporating ring-constrained amino acid surrogates with specific spatial configurations, while the overall molecular complexity is managed through systematic design of peptide constructs with defined structural motifs
Solution Approach 2:
The invention introduces ring-constrained surrogates at specific positions within the peptide sequence where local structural modifications maximize receptor binding affinity, rather than uniformly increasing complexity throughout the entire molecule
Data Source
AI summary
Linear constructs with an N-terminus and a C-terminus which bind to a natriuretic peptide receptor and include a plurality of amino acid residues and at least one amino acid surrogate of formula I:where R, R′, Q, Y, W, Z, J, x and n are as defined in the specification, and optionally at least one prosthetic group covalently bound to a reactive group of at least one of the amino acid residues or surrogates, pharmaceutical compositions including such linear constructs, and methods of treating congestive heart failure or other conditions, syndromes or diseases for which induction of anti-hypertensive, cardiovascular, renal or endocrine effects are desired.