hNGAL Muteins for CGRP Binding Specificity
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Solution Overview
Problem
There is a need for specific compounds that can recognize and bind to calcitonin gene-related peptide (CGRP) to modulate its activity, which is essential for diagnostic screening and therapeutic intervention in disease states associated with CGRP activity, as CGRP is involved in various biological activities including migraines and vascular tone regulation.
Innovation Solution
The development of muteins derived from human lipocalin 2 (hNGAL) that exhibit detectable affinity and specificity for CGRP, achieved through amino acid substitutions and mutations, allowing them to bind effectively to both human and rat CGRP isoforms, thereby modulating their biological activities.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing CGRP treatments are used, then CGRP activity is inhibited, but cardiovascular side effects occur
Solution Approach 1:
The patent modifies the binding parameters of the lipocalin protein through amino acid substitutions, creating muteins with altered specificity for CGRP. This allows selective inhibition of CGRP activity while maintaining different pharmacological properties that reduce cardiovascular side effects compared to existing treatments
2Measurement precision
If high specificity for CGRP is achieved, then diagnostic and therapeutic accuracy improves, but compound development complexity increases
Solution Approach 1:
The patent introduces specific local modifications (amino acid substitutions) at particular positions within the lipocalin protein sequence. These localized changes confer high specificity for CGRP binding while maintaining the overall protein structure and simplifying the development process compared to creating entirely new molecules
Data Source
AI summary
The present disclosure provides hNGAL muteins that bind CGRP and can be used in various application including pharmaceutical applications, for example, migraine. The present disclosure also concerns methods of making one or more muteins described herein as well as compositions and combinations comprising one or more of such muteins. The present disclosure further relates to nucleic acid molecules encoding such muteins and to methods for generation of such muteins and nucleic acid molecules. In addition, the application discloses therapeutic and/or diagnostic uses of these muteins as well as compositions and combinations comprising one or more of such muteins.