Halogenated Biotin Dimer for Targeted Astatine-211 Delivery
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing biotin-based drug delivery systems face issues with immunogenicity and non-specific binding, limiting their effectiveness in imaging diagnosis and treatment, particularly for colorectal cancer.
Innovation Solution
A biotin-modified dimer is developed, combined with a mutant streptavidin, to create a Cupid-Psyche system for targeted delivery of alpha-radionuclide astatine-211 ( 211< At) using a Cupid-binding single chain variable fragment (scFv)-type antibody, enhancing specificity and stability for colorectal cancer treatment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If a single-stranded DNA probe is used for detecting complementary sequences, then the detection simplicity is maintained, but the binding affinity and detection sensitivity are insufficient
Solution Approach 1:
The patent combines two single-stranded DNA sequences to form a double-stranded DNA probe structure. This merging of two separate strands creates a probe with enhanced binding affinity while maintaining the simplicity of single-stranded sequence design, thereby improving detection sensitivity without significantly increasing overall complexity
Solution Approach 2:
The patent performs preliminary synthesis of two specific single-stranded DNA sequences that are complementary to each other and to the target sequence. By preparing these strands in advance with predetermined complementary bases, the probe achieves high binding affinity when hybridized to the target, resolving the sensitivity issue before detection occurs
2Reliability
If conventional DNA probes without modifications are used, then the manufacturing process is simple, but the probe stability and detection accuracy are insufficient
Solution Approach 1:
The patent introduces biotin modifications at specific positions (5' and/or 3' ends) of the DNA strands, changing the chemical parameters of the probe. This modification enhances probe stability and detection accuracy through biotin-streptavidin interaction, while the modification process remains manageable through standardized conjugation methods
Solution Approach 2:
The patent uses biotin as an intermediary molecule that can be covalently attached to the DNA strands. This intermediary provides enhanced stability and detection capability through its high-affinity interaction with streptavidin, while the attachment process follows conventional chemical conjugation protocols that maintain manufacturing feasibility
3Productivity
If DNA probes are used for detecting complementary sequences, then the detection capability is provided, but the probe preparation time and cost are excessive
Solution Approach 1:
The patent segments the probe design into two separate single-stranded DNA sequences that can be synthesized independently and then combined. This segmentation allows for parallel preparation of complementary strands, reducing overall preparation time while maintaining the enhanced binding capabilities of the double-stranded probe structure
Solution Approach 2:
The patent creates a universal probe design where the two single-stranded sequences can be synthesized using standard DNA synthesis protocols and then combined to form a functional double-stranded probe. This multi-functional approach allows the same synthesis methodology to produce probes with enhanced stability and detection capability, improving productivity without proportionally increasing time or cost
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 system efficiently delivers 211< At to colorectal cancer cells, reducing immunogenicity and background noise, enabling effective imaging and treatment with high specificity and stability.
Implementation Method 1
the biotin moiety of the second strand is used to bind to a streptavidin molecule
Data Source
Figure 1~2
Figure 3~4
Figure 5
AI summary
It is an object of the present invention to provide a novel halogenated biotin-modified dimer capable of performing imaging diagnosis or treatment. According to the present invention, a compound represented by the following formula (1) or a salt thereof is provided: wherein L1 represents a trivalent linking group, L2 represents a divalent linking group, Hal represents a halogen, p represents an integer of 1 to 5, and q, r, s, and t each independently represent an integer of 1 to 8.