PACAP Peptide Tetrazole Modification for Protease Resistance

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Solution Overview

Problem

PACAP peptides are unstable in aqueous solutions, leading to a short half-life in the body due to lack of protease resistance.

Innovation Solution

The stability of PACAP peptides is enhanced by replacing the carboxy group of aspartic acid with tetrazole, maintaining affinity for PAC1R, VPAC1R, and VPAC2R receptors.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If PACAP peptide is used as a pharmaceutical drug, then neuroprotective activity and physiological effects are achieved, but stability in aqueous solution deteriorates and half-life in the body becomes short due to lack of protease resistance

Engineering Contradiction:

Improveneuroprotective activityVSAvoidstability in aqueous solution

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent applies parameter changes by substituting specific amino acid residues in the PACAP peptide sequence with chemically modified amino acids that have enhanced protease resistance. This modifies the chemical parameters of the peptide while preserving its biological activity, directly resolving the contradiction between maintaining neuroprotective activity and improving stability in aqueous solution.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite peptide structure by combining PACAP with chemically modified amino acid residues that provide protease resistance. This composite approach integrates the neuroprotective properties of PACAP with the stability characteristics of the modified amino acids, simultaneously achieving both reliability and compositional stability.

Inventive Principle:

Principle #40Composite materials

2Reliability

If PACAP peptide is used as a pharmaceutical drug, then neuroprotective activity and physiological effects are achieved, but half-life in the body becomes short due to lack of protease resistance

Engineering Contradiction:

Improveneuroprotective activityVSAvoidhalf-life in the body

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent modifies the chemical parameters of the PACAP peptide by incorporating protease-resistant amino acid substitutions. This changes the peptide's resistance to enzymatic degradation, directly extending its half-life in the body while preserving its neuroprotective activity and physiological effects.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent applies beforehand cushioning by pre-modifying the PACAP peptide structure with protease-resistant amino acid residues before administration. This preemptive modification protects the peptide from enzymatic degradation in the body, ensuring prolonged duration of action and sustained neuroprotective effects.

Inventive Principle:

Principle #11Beforehand cushioning (Prior cushioning)

Data Source

PatentUS12304932B2PACAP stabilized peptide

Publication Date: 2025.05.20 SENJU PHARMA CO LTD

AI summary

The purpose of the present invention is to provide a PACAP peptide having increased stability. The problem is solved by the discovery that substituting a carboxy group of the position 3 and/or position 8 aspartic acid in the PACAP sequence by tetrazole significantly enhances stability.