Cyclic Peptides Modulating CD36 for Atherosclerosis

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Solution Overview

Problem

There is a need for novel modulators of CD36 to treat pathological conditions associated with dysregulated or unregulated CD36 activity, which are linked to various diseases such as atherosclerosis, inflammation, and other metabolic disorders.

Innovation Solution

Development of cyclic peptides that specifically modulate CD36 activity by binding to CD36 and inhibiting its signaling pathways, thereby reducing inflammatory responses and pathological conditions associated with CD36 dysregulation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If cyclic peptides are designed to specifically bind and inhibit CD36, then therapeutic efficacy for treating CD36-related diseases is improved, but the complexity of peptide synthesis and structural design increases

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidpeptide synthesis complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The cyclic peptide is designed with a segmented structure comprising specific amino acid sequences that can be synthesized using standard solid-phase peptide synthesis methods. The peptide includes defined regions for CD36 binding (containing hydrophobic and aromatic residues) and cyclic structure formation, allowing modular synthesis and assembly of the therapeutic agent.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention optimizes specific parameters of the cyclic peptide including molecular weight (500-2000 Da), hydrophobicity index (2.0-4.0), and cyclic structure stability to achieve effective CD36 inhibition. These parameter optimizations enable the peptide to bind CD36 with high affinity while maintaining synthesizability using conventional methods.

Inventive Principle:

Principle #35Parameter changes

2Adaptability or versatility

If cyclic peptides are designed with high specificity for CD36 binding, then selectivity for CD36-mediated pathways is improved, but the difficulty of optimizing binding affinity and specificity increases

Engineering Contradiction:

ImproveselectivityVSAvoidbinding optimization difficulty

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The cyclic peptide incorporates localized functional regions with specific amino acid properties: hydrophobic residues (Leu, Ile, Phe) positioned for core CD36 binding, aromatic residues (Trp, Tyr, Phe) for pi-stacking interactions with CD36 ligands, and polar residues (Ser, Thr) for hydrogen bonding. This local quality differentiation enables high selectivity for CD36 while simplifying the optimization process through rational design.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The cyclic peptide adopts an asymmetric three-dimensional conformation that complements the asymmetric binding site on CD36. The peptide contains chiral centers with specific stereochemistry (L-amino acids in defined configurations) that create a non-superimposable mirror image structure, enhancing binding specificity through stereoselective interactions with CD36 while maintaining synthesizability.

Inventive Principle:

Principle #4Asymmetry

Data Source

PatentUS11879021B2Cyclic peptides and uses thereof

Publication Date: 2024.01.23 VALORISATION RECHERCHE LIMITED PARTNERSHIP

AI summary

Novel cyclic peptide GHRP-6 analogs of formula (I): (I) or pharmaceutically acceptable esters or salts thereof, are described. These cyclic peptide GHRP-6 analogs may be used for modulating CD36 activity, for example for the treatment of CD36-related diseases, disorders or conditions in a subject, such as atherosclerosis and age-related macular degeneration.