Boron Compounds Inhibiting Protein Cross-Linking
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Solution Overview
Problem
Current treatments for diseases caused by abnormal protein cross-linking, such as Alzheimer's disease, Parkinson's disease, and Celiac disease, lack effective inhibitors for transglutaminase activity, which contributes to these conditions.
Innovation Solution
Development of a series of boron compounds represented by specific formulas that inhibit protein cross-linking, acting as prophylactic and therapeutic agents for diseases like Alzheimer's disease, Parkinson's disease, Celiac disease, and others by targeting abnormal protein aggregation and transglutaminase activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If transglutaminase activity is not inhibited, then protein cross-linking proceeds abnormally, but no effective inhibitor has been available for therapeutic use
Solution Approach 1:
The patent modifies the molecular structure of boronic acid compounds by changing parameters such as substituent groups (R1-R6), ring structures, and positional arrangements to optimize transglutaminase inhibition activity. This involves systematic variation of chemical parameters to achieve potent and selective inhibition of abnormal protein cross-linking
Solution Approach 2:
Boronic acid compounds act as intermediary substances that bind to transglutaminase active sites, preventing the enzyme from catalyzing abnormal protein cross-linking reactions. The boronic acid group forms a reversible covalent bond with the active site serine residue, serving as a molecular intermediary that blocks harmful enzymatic activity
2Adaptability or versatility
If boron compounds are developed as transglutaminase inhibitors, then new therapeutic options are available, but no such inhibitors have been reported heretofore
Solution Approach 1:
The boronic acid compounds exhibit universal applicability across multiple disease conditions caused by abnormal protein cross-linking, including Alzheimer's disease, Parkinson's disease, cataract, and other neurodegenerative disorders. A single class of compounds can address diverse pathologies through the common mechanism of transglutaminase inhibition
Solution Approach 2:
The patent systematically varies chemical parameters of boronic acid derivatives to create a library of compounds with different potencies, selectivities, and pharmacokinetic properties, enabling selection of optimal candidates for different therapeutic indications
Data Source
AI summary
The present invention provides a protein cross-linking inhibitor containing a compound represented by any of the following formulas (1)-(13), or a pharmaceutically acceptable salt thereof:R3—[—X—B(ZR1)—Y—B(ZR2)—W—]n—R4, (1)R3—[—X—B(ZR1)—Y—]n—R4, (2)R3—[—B(ZR1)—Y—B(ZR2)—W—]n—R4, (3)R3—[—X—B(ZR1)—]n—R4, (4)R3—[—B(ZR2)—W—]n—R4, (5)R3—X—B(ZR1)-T[B(ZR2)—W—R4]2, (6)R3—B(OH)2, (7)R3—B(ZR1)—X—B(ZR2)—R4, (8)R3—B(R1)—O—B(R2)—R4, (9)R3—[—X—B(ZR1)—Y—B(ZR2)—]n—R4, (10)R3—[—X—B(ZR1)—Y—B(ZR2)—W-Q-]n—R4, (11)R3—[—P—X—B(ZR1)—Y—B(ZR2)—W—]n—R4, (12)[R3—X—B(ZR1)—Y]2B(ZR2), (13)wherein each symbol is as defined in the DESCRIPTION.