AFP Peptides Inhibit Estrogen-Dependent Cell Proliferation
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Solution Overview
Problem
Current peptides derived from alpha-fetoprotein (AFP) with fewer than eight residues have lost anti-estrotrophic activity, making it difficult to develop effective lead compounds for treating estrogen-dependent cancers, and the specific binding mechanism of AFP and its peptides is not well understood.
Innovation Solution
Development of small peptides, specifically four to seven amino acids in length, derived from the active site of alpha-fetoprotein with unique amino acid modifications, such as TOVNOGNEK, that retain anti-estrotrophic activity, including linear, polymeric, and multimeric forms, and their use in pharmaceutical compositions to inhibit estrogen-dependent cell growth.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If peptide length is reduced to fewer than eight residues, then ease of manufacture and synthesis is improved, but anti-estrotrophic activity is lost
Solution Approach 1:
The patent applies parameter changes by systematically varying the amino acid sequence parameters within the 4-7 residue range to identify sequences that maintain anti-estrotrophic activity. Specific amino acid substitutions and modifications are made to optimize both the biological activity and synthesizability of the peptides, resolving the contradiction between reduced peptide length and retained functionality.
2Reliability
If unique amino acid modifications are introduced (such as TOVNOGNEK sequence), then anti-estrotrophic activity is enhanced, but manufacturing complexity increases
Solution Approach 1:
The patent applies local quality by introducing specific amino acid modifications at particular positions within the peptide sequence (such as the TOVNOGNEK sequence). These localized modifications enhance anti-estrotrophic activity while minimizing overall structural complexity, allowing the peptide to maintain functionality without excessive manufacturing complexity.
3Reliability
If peptide sequences are optimized for activity, then binding mechanism effectiveness is improved, but understanding of binding mechanism remains insufficient
Solution Approach 1:
The patent applies segmentation by breaking down the AFP sequence into smaller peptide fragments (4-7 residues) to systematically identify the minimal active sequence. This segmentation approach allows for optimized binding effectiveness through sequence variation while generating information about binding mechanisms through structure-activity relationship analysis of the segmented peptides.
Data Source
AI summary
The invention relates to compounds that include peptides that inhibit estrogen receptor dependent cell proliferation. The compounds of the invention are useful for treating cell proliferative disorders or physiological conditions characterized by undesirable or unwanted estrogen induced cell proliferation, including breast cancer.