C5-Binding Polypeptide Sequence Modifications for Stable Activity
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Solution Overview
Problem
Existing C5 binding polypeptides suffer from stability issues, which affect their efficacy in therapeutic applications, despite retaining biological activity such as binding affinity for human complement component 5 (C5) and inhibition of the complement pathway.
Innovation Solution
Modifying specific amino acid residues in the C5 binding polypeptides, particularly at positions 52 and 53, and optionally at position 60, improves stability while maintaining biological activity, including binding affinity for C5 and inhibition of the complement pathway.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If C5 binding polypeptides are used for therapeutic applications, then binding affinity for C5 and inhibition of complement pathway is achieved, but stability is insufficient
Solution Approach 1:
The patent applies parameter changes by modifying specific amino acid residues at positions 52 and 53 in the C5 binding polypeptide sequence. These sequence modifications alter the physical-chemical parameters of the polypeptide, resulting in improved stability while preserving the binding affinity for C5 and therapeutic efficacy in inhibiting the complement pathway.
2Stability of the object's composition
If amino acid residues are modified to improve stability, then stability increases, but biological activity may be affected
Solution Approach 1:
The patent applies local quality by making targeted modifications at specific local positions (amino acid residues 52 and 53) within the polypeptide sequence. These localized changes improve overall stability without disrupting the critical binding regions, thereby maintaining biological activity including C5 binding affinity and complement pathway inhibition.
Data Source
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AI summary
The invention relates to a polypeptide capable of binding human complement component 5 (C5), said polypeptide comprising the amino acid sequence [BM]-[L2]-QSX42X43LLX46EAKKLX52X53X54Q wherein [BM] is a C5 binding motif; [L2] is an interconnecting loop; X42 is selected from A and S; X43 is selected from N and E; X46 is selected from A, S and C; X52 is selected from E, N and S; X53 is selected from D, E and S, provided that X53 is not D when X52 is N; and X54 is selected from A and S.