Clearing Agent for Streptavidin Mutant Removal
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Solution Overview
Problem
There is a need for an effective method to promptly remove a streptavidin mutant with reduced affinity to natural biotin from the body after its administration, as part of a pretargeting method for therapeutic and diagnostic applications, to prevent non-specific accumulation and associated side effects.
Innovation Solution
A clearing agent is developed, which comprises a compound that binds to a biotin variant dimer through linking groups, facilitating the removal of the streptavidin mutant and molecular probe fusion from the body by exploiting the high affinity between the biotin variant and the streptavidin mutant.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a streptavidin mutant with reduced affinity to natural biotin is used in pretargeting therapy, then the binding specificity to target sites is improved, but the clearance speed from non-target sites deteriorates
Solution Approach 1:
A biotin variant compound is introduced as an intermediary substance that selectively binds to the streptavidin mutant in the blood circulation. This intermediary compound facilitates the removal of the streptavidin mutant from non-target sites while preserving the streptavidin's binding specificity to target sites, thus resolving the contradiction between binding specificity and clearance speed.
Solution Approach 2:
The invention changes the chemical parameters of the biotin molecule by creating a biotin variant with modified binding characteristics. This parameter change allows the biotin variant to have high affinity for the streptavidin mutant while maintaining compatibility with the streptavidin's target site binding, enabling selective clearance without compromising binding specificity.
2Reliability
If the streptavidin mutant remains in the body after administration, then therapeutic effect is maintained, but non-specific accumulation and side effects increase
Solution Approach 1:
The invention extracts the harmful component (streptavidin mutant) from the body through selective binding with the biotin variant compound. The biotin variant compound specifically targets and removes the streptavidin mutant from circulation, separating the therapeutic function from the harmful non-specific accumulation, thus maintaining therapeutic effect while eliminating side effects.
Solution Approach 2:
The invention converts the potential harm of the streptavidin mutant's persistence into a benefit by utilizing its binding affinity for the biotin variant compound. The same binding affinity that ensures therapeutic effect is leveraged to enable selective removal of the streptavidin mutant from non-target sites, transforming the potential harmful persistence into a beneficial clearance mechanism.
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
The clearing agent efficiently removes the streptavidin mutant and molecular probe fusion from the body, reducing non-specific accumulation and enhancing the accuracy of diagnostic and therapeutic outcomes by ensuring timely clearance of the fusion from non-target sites.
Implementation Method 1
the interaction of avidin/streptavidin with biotin has been broadly applied in the field of biochemistry, molecular biology or medicine
Implementation Method 2
a compound, in which a plurality of sugar residues bind to the biotin variant dimer described in International Publication No. WO 2015/125820 via linking groups
Data Source
AI summary
It is an object of the present invention to provide a clearing agent, by which after a fusion of the streptavidin mutant and a molecular probe has been administered, the fusion, which is not localized in a target site such as an affected site but remains in the body, can be promptly removed (cleared) from the body. The present invention provides a compound represented by the following formula (1) or a salt thereof:wherein X1a, X1b, X2a and X2b each independently represent O or NH; Y1 and Y2 each independently represent C or S; Z1 and Z2 each independently represent O, S or NH; V1 and V2 each independently represent S or S+—O−; n1 and n2 each independently represent an integer of 0 or 1; L10 and L12 each independently represent a divalent linking group; L11 represents a trivalent linking group; L14 represents a divalent linking group; and Sugar represents a sugar residue.