Application of compound or medicinal derivative thereof in inhibition of AIM2 protein activity
A protein activity and compound technology, applied in the field of inhibiting AIM2 protein activity, compound or its pharmaceutical derivatives, can solve the problem of expensive biological agents, unsatisfactory long-term effect of immunomodulators, and increased risk of psoriasis recurrence and other issues, achieve considerable long-term effects, increase applicability and aesthetics, and be applicable to a wide range of people
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Embodiment 1
[0099] Example 1 Interaction mode between SLD-1 and AIM2 protein
[0100] The structure of SLD-1 combined with AIM2 protein was simulated: first, two rounds of binding simulations were performed using the Surflex module in the Sybyl-X2.1 software, and then multiple strands were formed by combining with Arg24, Leu72, Asn73 and other amino acids on AIM2. Hydrogen bonding interactions were manually screened and reviewed. The result is as Image 6 As shown, SLD-1 interacts with multiple hydrophobic amino acids, such as Arg24 (hydrophobic part of side chain), Lys26 (hydrophobic part of side chain), Phe27, Phe28, Leu40, His41, Lys71 (hydrophobic part of side chain) and Leu72 Strong hydrophobic interactions occur. In addition, compound SLD-1 formed π-π stacking interactions with Phe27 and Phe28. It can be seen that interactions such as hydrophobic π-π stacking jointly maintain the binding of compound SLD-1 to protein AIM2.
Embodiment 2
[0101] Example 2 SLD-1 and AIM2 human protein have strong affinity test
[0102] In the examples of the present invention, the affinity between SLD-1 and AIM2 human protein was detected: first, the pET28A vector was used to express and purify the human full-length AIM2 protein; Methods The CM5 chip amino-coupling method was used to determine the affinity. Test results such as Figure 7 As shown, the results show that SLD-1 specifically binds to human AIM2 protein, the binding constant is 1.029E-5M, and the binding ability is very strong.
Embodiment 3
[0103] Example 3 SLD-1 and AIM2 murine protein have strong affinity test
[0104] In the examples of the present invention, the affinity between SLD-1 and AIM2 murine protein was detected: first, the pET28A vector was used to express and purify the full-length murine AIM2 protein; then the surface plasmon resonance (SPR) of Biacore was used Methods The CM5 chip amino-coupling method was used to determine the affinity. Test results such as Figure 8 As shown, the results show that SLD-1 specifically binds to murine AIM2 protein, the binding constant is 1.033E-5M, and the binding ability is very strong.
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