PYY Analogues for Appetite Suppression and Metabolic Regulation
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Solution Overview
Problem
Current treatments for obesity and diabetes, such as pharmacotherapy and weight loss surgery, come with adverse side effects and limited efficacy, and there is a need for compounds that can effectively reduce food intake and alter energy metabolism with improved potency and duration of action.
Innovation Solution
Development of PYY analogues with specific amino acid substitutions or deletions that decrease food intake, caloric intake, and alter energy metabolism, which can be administered alone or in combination with GLP-1 analogues to enhance appetite suppression and metabolic effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If pharmacotherapy or weight loss surgery is used to treat obesity and diabetes, then weight loss and metabolic improvement can be achieved, but serious adverse side effects and limited efficacy occur
Solution Approach 1:
The patent applies parameter changes by modifying the amino acid sequence of PYY to create analogues with improved properties. Specifically, the patent introduces substitutions at positions 3, 6, 7, 10, 11, 12, 13, 14, 15, 16, 18, 19, 22, 23, 25, 26, 27, 30, and 31, as well as deletions of specific residues, to enhance potency and duration of action while reducing side effects. This directly addresses the contradiction by changing the molecular parameters of the therapeutic agent.
Solution Approach 2:
The patent employs composite materials by creating chimeric peptides that combine portions of PYY with other peptide sequences. The invention describes compounds comprising an N-terminal portion (residues 1-10 or 1-15 of PYY), a linker sequence, and a C-terminal portion (residues 20-36 of PYY), forming a composite structure that leverages the beneficial properties of different segments while mitigating limitations of the native peptide.
2Duration of action of moving object
If PYY analogues are developed to improve potency and duration of action, then appetite suppression and metabolic regulation are enhanced, but the complexity of the compound structure increases
Solution Approach 1:
The patent applies segmentation by dividing the PYY molecule into distinct functional segments: an N-terminal segment (residues 1-10 or 1-15), a middle segment containing the DPP-IV cleavage site, and a C-terminal segment (residues 20-36). This segmentation allows independent optimization of each region for stability, activity, and half-life, thereby extending duration of action through strategic modification of specific segments rather than the entire molecule.
Solution Approach 2:
The patent employs preliminary action by pre-modifying the PYY sequence with stabilizing amino acid substitutions and protective deletions before administration. Specifically, the deletion of residues susceptible to enzymatic degradation and the introduction of protease-resistant amino acids are performed in advance to extend the in vivo half-life and duration of action of the analogue.
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 PYY analogues exhibit improved potency, longer duration of action, and reduced side effects, allowing for more convenient and effective weight management and metabolic regulation, including improved insulin release and carbohydrate metabolism.
Implementation Method 1
PYY 3-36 binds to the Y2 receptor of the Y family of receptors
Data Source
AI summary
PYY-derived compounds comprising residues changed from the naturally-occurring peptide sequence and substituted, for example at their gamma-carboxylic acid groups, epsilon-amino groups or alpha-amino groups, with fatty dioic acid groups either directly or via short pendant oligopeptides. Related methods, compositions and uses, in particular for use in appetite suppression and the treatment or prevention of diabetes or obesity