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SERS and MD simulat...
SERS and MD simulation studies of a kinase inhibitor demonstrate the emergence of a potential drug discovery tool
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Karthigeyan, Dhanasekaran (författare)
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Siddhanta, Soumik (författare)
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Kishore, Annavarapu Hari (författare)
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- Perumal, Sathya S. R. R. (författare)
- KTH,Teoretisk kemi och biologi
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- Ågren, Hans (författare)
- KTH,Teoretisk kemi och biologi
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Sudevan, Surabhi (författare)
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Bhat, Akshay V. (författare)
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Balasubramanyam, Karanam (författare)
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Subbegowda, Rangappa Kanchugarakoppal (författare)
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Kundu, Tapas K. (författare)
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Narayana, Chandrabhas (författare)
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(creator_code:org_t)
- 2014-06-27
- 2014
- Engelska.
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 111:29, s. 10416-10421
- Relaterad länk:
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https://www.pnas.org...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- We demonstrate the use of surface-enhanced Raman spectroscopy (SERS) as an excellent tool for identifying the binding site of small molecules on a therapeutically important protein. As an example, we show the specific binding of the common antihypertension drug felodipine to the oncogenic Aurora A kinase protein via hydrogen bonding interactions with Tyr-212 residue to specifically inhibit its activity. Based on SERS studies, molecular docking, molecular dynamics simulation, biochemical assays, and point mutation-based validation, we demonstrate the surface-binding mode of this molecule in two similar hydrophobic pockets in the Aurora A kinase. These binding pockets comprise the same unique hydrophobic patches that may aid in distinguishing human Aurora A versus human Aurora B kinase in vivo. The application of SERS to identify the specific interactions between small molecules and therapeutically important proteins by differentiating competitive and noncompetitive inhibition demonstrates its ability as a complementary technique. We also present felodipine as a specific inhibitor for oncogenic Aurora A kinase. Felodipine retards the rate of tumor progression in a xenografted nude mice model. This study reveals a potential surface pocket that may be useful for developing small molecules by selectively targeting the Aurora family kinases.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology (hsv//eng)
Nyckelord
- vibrational spectroscopy
- structure-activity relationship
- ligand binding
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Karthigeyan, Dha ...
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Siddhanta, Soumi ...
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Kishore, Annavar ...
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Perumal, Sathya ...
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Ågren, Hans
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Sudevan, Surabhi
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visa fler...
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Bhat, Akshay V.
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Balasubramanyam, ...
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Subbegowda, Rang ...
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Kundu, Tapas K.
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Narayana, Chandr ...
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