Modified AKT-Inhibitory Peptides for Targeted Kinase Modulation
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Solution Overview
Problem
Current therapies lack effective agents to modulate the activity of AKT, a key kinase involved in various human diseases including cancer, neurodegenerative disorders, and psychiatric disorders.
Innovation Solution
Development of modified peptides, such as (X)-GRT-(Y)-TLC-(Z), which target the catalytic activity of AGC family kinases like AKT, to inhibit their activity and modulate cellular functions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapies are used, then treatment of diseases is provided, but effective agents to modulate AKT activity are lacking
Solution Approach 1:
The patent modifies peptide sequences and chemical structures to change binding parameters, creating variants with different affinities and specificities for AKT kinase. This allows effective modulation of AKT activity while maintaining therapeutic reliability through optimized molecular parameters
2Adaptability or versatility
If modified peptides are developed to target AKT catalytic activity, then AKT activity modulation is achieved, but device complexity increases
Solution Approach 1:
The patent divides the AKT-binding interface into discrete peptide segments and motifs that can be independently optimized. By segmenting the binding interface, the patent achieves effective AKT inhibition through modular peptide designs rather than requiring complex full-length protein structures
Solution Approach 2:
The patent creates simplified peptide copies and mimics of natural AKT-binding sequences. These copied and optimized peptide motifs replicate the functional binding capability while reducing structural complexity compared to native protein-protein interactions
Data Source
AI summary
The present disclosure relates to a modified peptide including (i) an amino acid sequence (X)-GRT-(Y)-TLC-(Z), or (ii) an amino acid sequence having at least 40% sequence identity to the amino acid sequence (X)-GRT-(Y)-TLC-(Z), wherein X, Y, and Z are the same as described in the specification. In this regard, methods for inhibiting the activity of at least one enzyme selected from the group consisting of AKT1 (PKB alpha), AKT2 (PKB beta), MAP3K8 (COT), MST4, AURKB (Aurora B), ROCK1, RPS6KB1 (p70S6K), CDC42 BPA (MRCKA), BRAF, RAFI (cRAF) Y340D Y341D, SGK (SGK1), MAP4K4 (HGK), AURKA (Aurora A), AURKC (Aurora C), BRAF V599E, CHEK1 (CHK1), GSG2 (Haspin), CHEK2 (CHK2), FGR, IKBKB (IKK beta), CDK7/cyclin H/MNAT1, and CDC42 BPB (MRCKB) and Ab!; and inhibiting cell proliferation are also provided, as are methods for preventing or treating cancer or a neurodegenerative disease or disorder.