Pseudofactin II Derivatives Synthesis via Solid Phase Cyclization

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Solution Overview

Problem

Current methods for producing pseudofactin II derivatives lack high yield and purity, and there is a need for effective biosurfactants that can reduce hydrophobicity and prevent microbial colonization on surfaces and in medical and industrial applications.

Innovation Solution

A novel method of solid phase synthesis (SPPS) is developed to produce pseudofactin II derivatives with varying alkyl chain lengths and amino acids, involving carbodiimide-mediated peptide synthesis, internal cyclization, and careful protection group management to achieve high yield and purity, enabling the derivatives to act as effective biosurfactants for surface protection and microbial inhibition.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If current methods for producing pseudofactin II derivatives are used, then production can be achieved, but yield and purity are not high

Engineering Contradiction:
ImprovepurityVSAvoidyield
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The synthesis process is divided into distinct stages: solid-phase peptide synthesis to generate linear precursors, followed by solution-phase cyclization to form the final cyclic lipopeptide structure. This segmentation allows optimization of each stage independently, achieving both high yield and high purity

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The linear peptide precursor is synthesized first with protected side chains using solid-phase synthesis, preparing the molecule in advance for the cyclization step. This preliminary action ensures the precursor is ready for efficient cyclization, improving overall yield and purity of the final product

Inventive Principle:
Principle #10Preliminary action

2Object-affected harmful factors

If pseudofactin II derivatives are synthesized to reduce hydrophobicity, then surface protection against microbial colonization is achieved, but synthesis complexity increases

Engineering Contradiction:
Improvemicrobial colonizationVSAvoidsynthesis complexity
Core Design Contradiction:
Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

Solid-phase synthesis resin serves as an intermediary support during peptide synthesis, enabling systematic assembly of amino acid sequences with controlled side chain protection. This intermediary approach simplifies the complex synthesis process by providing a structured platform for building the cyclic lipopeptide structure

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The synthesis employs controlled changes in protection group status (protected vs. deprotected side chains) and molecular conformation (linear vs. cyclic) to achieve the desired biosurfactant properties. These parameter changes enable precise control over the final product's hydrophobicity and antimicrobial activity

Inventive Principle:
Principle #35Parameter changes

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 synthesized pseudofactin II derivatives demonstrate enhanced stability and solubilizing capacity, effectively reducing microbial biofilm formation and preventing colonization on surfaces, while also serving as carriers for hydrophobic and hydrophilic compounds, enhancing their applications in medicine, industry, and environmental remediation.

Implementation Method 1

solid phase synthesis of the peptide R-Gly-Ser(tBu)-Thr-Leu-Leu-X-Leu-Leu-OH by the carbodiimide method

Methodology Applied
Scientific EffectCarbodiimide-mediated peptide synthesis: Chemical Bonding

Implementation Method 2

internal cyclization of the peptide by the formation of an ester bond between the hydroxyl group of the side chain of L-threonine and the carboxyl group of the terminal L-leucine

Methodology Applied
Scientific EffectEster bond formation: Chemical Bonding

Implementation Method 3

The micellar solutions of biosurfactants are capable of solubilizing compounds, i.e. carry hydrophobic substances (hardly soluble or insoluble in water) to the biosurfactant solution at concentrations exceeding CMC

Methodology Applied
Scientific EffectSurfactant action: Surfactant

Implementation Method 4

The micellar solutions of biosurfactants are capable of solubilizing compounds

Methodology Applied
Scientific EffectMicelle formation: Microemulsion

Implementation Method 5

as compounds which reduce hydrophobicity and thus protects catheters, implants, lenses as well as tanks or reactors against colonization by microorganisms

Methodology Applied
Scientific EffectHydrophobicity reduction: Hydrophobe

Data Source

PatentEP3000821B1Pseudofactin derivatives, a method of synthesizing pseudofactin derivatives and their use
Publication Date: 2019.03.13 UNIV WROCLAWSKI
  • EP3000821B1 patent drawingFigure 1
  • EP3000821B1 patent drawingFigure 2
  • EP3000821B1 patent drawingFigure 3

AI summary

The invention relates to the synthesis of pseudofactin II derivatives by solid phase synthesis (SPPS), and their application. The synthesis includes solid phase synthesis of the peptide R-Gly-Ser(tBu)-Thr-Leu-Leu-X-Leu-Leu-OH by the carbodiimide method, where R denotes CH3(CH2)14 to CH3(CH2)22 and X denotes: Ala, Arg(Pbf), Asn(Trt), Asp(OtBu), Cys(Trt), Glu(OtBu), Gln(Trt), Gly, His(Trt), Ile, Leu, Lys(Boc), Met, Phe, Pro, Ser(tBu), Thr(tBu), Trp(Boc), Tyr(tBu), Val, cleavage of the peptide from the resin (while maintaining the tBu protecting group on the side chain of L-serine and the Pbf protecting group on the side chain of L-arginine, internal cyclization of the peptide (formation of an ester bond between the hydroxyl group on the side chain of L-threonine and the carboxyl group of L-leucine), removing the protecting groups located on the side chain of L-serine and L-arginine, and the purification of the obtained peptide.