BPLP-Derived Peptides for Metallo-ectopeptidase Inhibition
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Solution Overview
Problem
Current technologies lack effective inhibitors for membrane-bound metallo-ectopeptidases, particularly neutral endopeptidase (NEP) and aminopeptidase (APN), which are crucial for regulating pain perception and mineral ion balance, with existing inhibitors showing limited efficacy and specificity.
Innovation Solution
Development of peptides derived from human BPLP protein, specifically the QRFSR peptide, which acts as a potent inhibitor of NEP and APN, modulating nociceptive transmission and homeostatic exchanges by inhibiting the degradation of enkephalins and other neuropeptides.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing inhibitors are used for metallo-ectopeptidases, then some inhibitory activity is achieved, but efficacy and specificity are limited
Solution Approach 1:
The patent modifies the chemical structure parameters of existing inhibitors by introducing specific substituents at defined positions (e.g., R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, R22, R23, R24, R25, R26, R27, R28, R29, R30, R31, R32, R33, R34, R35, R36, R37, R38, R39, R40, R41, R42, R43, R44, R45, R46, R47, R48, R49, R50, R51, R52, R53, R54, R55, R56, R57, R58, R59, R60, R61, R62, R63, R64, R65, R66, R67, R68, R69, R70, R71, R72, R73, R74, R75, R76, R77, R78, R79, R80, R81, R82, R83, R84, R85, R86, R87, R88, R89, R90, R91, R92, R93, R94, R95, R96, R97, R98, R99, R100) to enhance both inhibitory efficacy and specificity for metallo-ectopeptidases
Solution Approach 2:
The patent creates composite inhibitor structures combining multiple functional groups and moieties (e.g., peptidic and non-peptidic components, aromatic rings, heterocyclic groups, charged and neutral regions) to achieve simultaneous high efficacy and specificity for metallo-ectopeptidase inhibition
2Adaptability or versatility
If peptides are designed to inhibit multiple metallo-ectopeptidases, then broader therapeutic coverage is achieved, but selectivity among different enzymes may be reduced
Solution Approach 1:
The patent designs peptides with universal binding features that allow them to inhibit multiple metallo-ectopeptidases (NEP, APN, DPP IV, cathepsin D) while maintaining therapeutic versatility for different indications including pain, depression, and mineral ion balance disorders
Solution Approach 2:
The patent incorporates specific local structural features (e.g., particular amino acid sequences, charged residues, aromatic groups at specific positions) that provide selective binding to conserved active site features of metallo-ectopeptidases, achieving both broad coverage and enzyme-specific recognition
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 QRFSR peptide effectively inhibits NEP and APN activity, providing analgesic and antidepressant effects by prolonging the action of endogenous opioids and maintaining mineral ion balance, offering a more potent and specific solution compared to existing dual inhibitors.
Implementation Method 1
The QRFSR peptide effectively inhibits NEP and APN activity, providing analgesic and antidepressant effects by prolonging the action of endogenous opioids
Data Source
AI summary
The invention relates to a peptide that is a maturation product of the Basic Prolin-rich Lacrinal Protein (BPLP) or a peptide derivative of said maturation product, wherein the peptide or peptide derivative exhibits an inhibitory property against a metallo-ectopeptidase, especially NEP and/or APN.The present invention also relates to polynucleotides coding for said peptides and to antibodies directed against said peptides. Furthermore, the present invention relates to diagnostic and therapeutic uses of human BPLP protein and inhibitory peptides derived therefrom, polypeptides coding for human BPLP protein or peptides derived therefrom as well as antibodies directed against BPLP protein or peptides derived therefrom.