Peptides Modulating Sperm Motility via PPP1 Complexes

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Solution Overview

Problem

Current male contraception methods are limited and invasive, and there is a need for non-invasive, reversible solutions that can modulate sperm motility without affecting hormonal control, as existing methods have side effects and are not ideal for treating male infertility.

Innovation Solution

Development of specific peptides that can modulate phosphoprotein phosphatase 1 complexes to increase or decrease sperm motility by translocating into the flagellum of spermatozoa, using cell-penetrating peptides linked to PPP1-modulatory sequences, such as H-GQQDQDRKVICFVAVSTLNV-NH2 and H-KPNATRPVTPPRVASGLNPSIQKASNYRNNTVLY-NH2, to disrupt interactions within sperm cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If hormonal-based male contraceptives are used to modulate sperm function, then sperm production control is achieved, but side effects occur and hormonal balance is disrupted

Engineering Contradiction:

Improvecontraceptive efficacyVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention extracts the specific function of sperm motility control from the overall hormonal regulation system. By targeting PPP1CC2 specifically in sperm cells rather than using systemic hormones, the contraceptive effect is isolated to sperm function only, leaving other hormonal systems unaffected and eliminating widespread side effects

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The invention uses small molecules as intermediaries that specifically bind to and modulate PPP1CC2 activity. These small molecules act as mediators between the administered compound and the phosphatase target, enabling precise control of sperm motility through phosphorylation state changes without requiring hormonal pathways

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If conventional therapeutic agents are used to treat sperm cells, then therapeutic effect is achieved, but the agents cannot penetrate the sperm plasma membrane due to lack of endocytotic pathways

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoiddrug delivery

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The invention employs cell-penetrating peptides as intermediary carriers that can traverse the sperm plasma membrane barrier. These peptides bind to the therapeutic small molecules and facilitate their entry into sperm cells through membrane translocation, overcoming the lack of conventional endocytotic pathways

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention creates a composite delivery system combining cell-penetrating peptides with therapeutic small molecules. This composite structure enables the therapeutic agent to overcome the membrane barrier while the small molecule maintains its specific PPP1CC2 modulatory activity once inside the cell

Inventive Principle:

Principle #40Composite materials

3Adaptability or versatility

If sperm motility is increased to treat infertility, then fertility is improved, but if sperm motility is decreased for contraception, then pregnancy is prevented

Engineering Contradiction:

Improvedual therapeutic and contraceptive applicationVSAvoidmodulation mechanism

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The invention creates a dynamic modulation system where PPP1CC2 activity can be adjusted in either direction depending on the administered compound. Activators increase phosphatase activity to promote dephosphorylation and enhance motility for infertility treatment, while inhibitors decrease phosphatase activity to increase phosphorylation and reduce motility for contraception

Inventive Principle:

Principle #15Dynamics

Solution Approach 2:

The invention changes the phosphorylation parameter of sperm proteins as the primary mechanism for controlling motility. By modulating the phosphorylation state through PPP1CC2 activity control, the system achieves reversible and bidirectional effects on sperm function without altering other physiological parameters

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 peptides effectively increase or decrease sperm motility by up to 95% or decrease non-motile sperm by up to 1.5-fold, providing a potential non-invasive, reversible male contraceptive and treatment for male infertility without affecting hormonal control or causing side effects.

Implementation Method 1

using cell-penetrating peptides linked to PPP1-modulatory sequences, such as H-GQQDQDRKVICFVAVSTLNV-NH2 and H-KPNATRPVTPPRVASGLNPSIQKASNYRNNTVLY-NH2, to disrupt interactions within sperm cells

Methodology Applied

Scientific EffectCell-penetrating peptide translocation:

Data Source

PatentEP3655424B1Peptides modulating sperm motility by modulating the phosphoprotein phosphatase 1 complex.

Publication Date: 2021.10.13 UNIVERSITY OF WOLVERHAMPTON

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Figure 2A~2D
Figure 2E~2H

AI summary

Novel peptides and the uses thereof, in particular for use in male contraception or for use in the treatment of male infertility.