Vasoactive Polypeptides for Selective Smooth Muscle Relaxation
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Solution Overview
Problem
Current therapeutic options for preventing vasospasm and its associated conditions, such as hypertension and stroke, lack specificity and often cause undesirable side effects like systemic hypotension, highlighting a need for effective smooth muscle relaxation methods without these drawbacks.
Innovation Solution
Development of smooth muscle relaxing polypeptides with specific amino acid sequences, including phosphoserine analogs and transduction domains, which can be administered alone or in combination with calcium channel blockers to promote vasorelaxation and prevent vasospasm, while minimizing systemic effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing therapeutic options are used to prevent vasospasm, then smooth muscle relaxation is achieved, but systemic hypotension occurs as an undesirable side effect
Solution Approach 1:
The patent applies local quality by designing polypeptides with specific amino acid sequences that target cerebral vascular smooth muscle selectively. The polypeptides contain cell-penetrating peptides (CPPs) that facilitate selective delivery to brain vessels, achieving local vasodilation in the cerebral circulation without causing systemic hypotension. This resolves the contradiction by making the therapeutic effect localized rather than generalized throughout the entire vascular system.
Solution Approach 2:
The patent employs parameter changes by modifying the amino acid sequence of the polypeptides to include specific phosphorylated residues and CPPs. These parameter changes in molecular structure enable selective penetration into cerebral vascular smooth muscle cells and activation of relaxation pathways specifically in the brain vasculature, thereby achieving vasospasm prevention without the harmful systemic hypotensive effects of conventional therapies.
2Reliability
If existing therapies are administered, then vasospasm symptoms are addressed, but lack of specificity for cerebral-selective responses occurs
Solution Approach 1:
The patent implements local quality through the incorporation of cell-penetrating peptides with specific amino acid sequences that exhibit affinity for cerebral vascular tissue. These CPPs enable the polypeptides to selectively penetrate and act on cerebral vascular smooth muscle cells, providing cerebral-selective vasodilation. This resolves the contradiction by confining the therapeutic action to the target organ (brain) while avoiding effects on other vascular beds.
Solution Approach 2:
The patent uses cell-penetrating peptides as intermediaries that facilitate selective delivery of the therapeutic polypeptides to cerebral vascular smooth muscle cells. The CPPs act as mediators that enable specific uptake and localization of the active polypeptide sequence in the brain vasculature, thereby achieving cerebral-selective treatment of vasospasm without affecting systemic circulation.
3Reliability
If smooth muscle relaxation is achieved through existing methods, then vasospasm is prevented, but undesirable side effects occur
Solution Approach 1:
The patent applies local quality by designing polypeptides that selectively relax smooth muscle in cerebral vessels through specific molecular interactions. The phosphorylated amino acid sequences and cell-penetrating peptides ensure that the relaxation effect is localized to the brain vasculature, preventing the generation of harmful side effects that occur with systemic smooth muscle relaxation in conventional therapies.
Solution Approach 2:
The patent converts the potential harm of non-specific smooth muscle relaxation into a benefit by using phosphorylated polypeptide sequences that specifically target cerebral vascular smooth muscle. The phosphorylation state and specific amino acid composition enable selective binding and activation in the brain vasculature, transforming what would be a harmful non-specific effect into a beneficial selective therapeutic action.
Data Source
AI summary
A polypeptide, a pharmaceutical composition including a polypeptide, and a method for treating a condition using a polypeptide are provided. The polypeptide includes an amino acid sequence according to the general formula X1-X2-X3, wherein X1 and X3 are independently absent or comprise a transduction domain, X2 includes Z3, and Z3 is selected from the group consisting of serine or phosphoserine analogs. The pharmaceutical composition includes a polypeptide including an amino acid sequence according to the general formula X1-X2-X3 and one or more components selected from the group consisting of a pharmaceutically acceptable carrier, a calcium channel blocker, and a combination thereof. X1 and X3 are independently absent or comprise a transduction domain, X2 includes Z3, and Z3 is selected from the group consisting of serine or phosphoserine analogs. The method of treating a condition includes administering a polypeptide including an amino acid sequence according to the general formula X1-X2-X3 to a subject in need thereof, wherein X1 and X3 are independently absent or comprise a transduction domain, X2 includes Z3, and Z3 is selected from the group consisting of serine or phosphoserine analogs. Also provided is a biomedical device including a polypeptide.