DBP Antagonist Peptides Block C5a Chemotaxis

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Solution Overview

Problem

Current technologies lack effective methods to block the enhancement of C5a/C5a des Arg-mediated chemotaxis and Ca2+ influx by Vitamin D Binding Protein (DBP), which contributes to immunoinflammatory disorders.

Innovation Solution

Development of novel DBP antagonist peptides corresponding to the N-terminal Domain I of DBP, which interfere with DBP's ability to enhance C5a/C5a des Arg-mediated chemotaxis and Ca2+ influx, utilizing specific amino acid sequences to inhibit DBP's biological activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If DBP is used to enhance C5a-mediated chemotaxis, then leukocyte recruitment is improved, but immunoinflammatory disorders are worsened

Engineering Contradiction:

Improvechemotaxis enhancementVSAvoidimmunoinflammatory disorders

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent segments the DBP molecule by identifying and isolating specific peptide sequences (amino acids 130-149 in Domain I) that are responsible for the harmful cochemotactic enhancement of C5a. By targeting only this specific segment rather than the entire DBP protein, the invention can selectively block the harmful function while potentially preserving other beneficial functions of DBP.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent introduces antagonist peptides as intermediary molecules that mediate between DBP and C5a/C5a des Arg. These antagonist peptides bind to DBP and prevent it from enhancing C5a-mediated chemotaxis, effectively acting as a blocking intermediary that stops the harmful signal transmission without requiring complete elimination of DBP.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Speed

If DBP enhances C5a chemotactic activity, then neutrophil and monocyte migration is improved, but Ca2+ influx and inflammation are worsened

Engineering Contradiction:

Improvecell migrationVSAvoidpro-inflammatory functions

Core Design Contradiction:

SpeedVSObject-generated harmful factors

Solution Approach 1:

The patent applies preliminary anti-action by administering DBP antagonist peptides before or during the inflammatory response to pre-block the harmful enhancement of C5a activity. The antagonist peptides are introduced in advance to prevent DBP from exerting its pro-inflammatory cochemotactic effects, thereby mitigating excessive cell migration and Ca2+ influx before they can cause significant tissue damage.

Inventive Principle:

Principle #9Preliminary anti-action

3Reliability

If full-length DBP is targeted to block chemotaxis, then C5a enhancement is inhibited, but vitamin D transport function may be affected

Engineering Contradiction:

Improvechemotaxis blockingVSAvoidDBP biological functions

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies local quality by designing antagonist peptides that specifically target the N-terminal Domain I region (amino acids 130-149) of DBP where the cochemotactic activity is located. This localized approach allows selective inhibition of the harmful C5a-enhancing function while leaving other domains of DBP (such as the vitamin D binding domain in the C-terminal region) intact and functional.

Inventive Principle:

Principle #3Local quality

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 DBP antagonist peptides effectively block DBP's enhancement of C5a/C5a des Arg chemotactic activity and Ca2+ influx, providing a therapeutic approach for treating immunoinflammatory disorders by inhibiting DBP-mediated biological functions.

Implementation Method 1

Novel DBP antagonist peptides derived from or corresponding to the DBP N-terminal Domain I have been isolated and synthesized. These peptides possess DBP antagonist properties including the ability to block, interfere with or prevent DBP from enhancing the C5a /C5a des Arg-mediated chemotaxis and Ca2+ influx

Methodology Applied

Scientific EffectProtein-protein binding:

Data Source

PatentUS7547676B2Antagonist peptides to the C5A chemotactic function of vitamin D binding protein

Publication Date: 2009.06.16 THE RES FOUND OF STATE UNIV OF NEW YORK

AI summary

It has been demonstrated that one of Vitamin D Binding Protein (DBP) biological functions is to enhance the chemotactic activity of C5a and C5a des Arg. The present invention has found that peptides having sequences that substantially correspond to a specific region in the N-terminal domain I of DBP can block the DBP enhancement of C5a or C5a des Arg chemotactic activity. Based in this discovery the present invention provides DBP antagonist peptides and the use thereof for the treatment C5a or C5a des Arg-mediated disorders.