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Duangrudee Tanramluk. Structure-based drug design approaches to improve Gleevec as promiscuous drug. (). King Mongkut's University of Technology North Bangkok. Central Library. : , 2019.
Structure-based drug design approaches to improve Gleevec as promiscuous drug
Name: Natsasion Srithiowat
Organization :
Mahidol University. Institute of Molecular Biosciences
Name: Duangrudee Tanramluk
Organization :
Mahidol University. Institute of Molecular Biosciences
Email :
duangrudee.tan@mahidol.ac.th
LCSH:
Chronic myeloid leukemia
-- Treatment
LCSH:
Imatinib
LCSH:
Drugs
-- Structure-activity relationships
Abstract:
Gleevec has revolutionized the treatment of chronic myeloid leukemia (CML). However, CML patients tends to experience relapse because Gleevec cannot eliminate CML stem cells. Previous study showed that disruption of p38-MAPK pathway can reduce CML stem cells survival. Therefore, we demonstrated an approach to develop a bispecific drug that may bind to both Abl1 kinase and p38-MAPK. By investigating the frequently occurring residues from 6 crystal structures of Gleevec-binding kinases, the drugs pyridine ring showed conserved interactions with the hinge region of all these kinases. Partial Least Square (PLS) method was used to analyze the distances between each equivalent residue pairs in the active sites. Distances that correlate with binding affinity (Kd) either by expansion or contraction of Gleevec molecule to enhance p38-MAPK binding were noted. Inter-molecular interactions between these kinases and Gleevec were analyzed using MANORAA.org. It showed that the tight binding kinase usually has more aromatic and hydrophobic interactions with Gleevecs pyridine ring. The determinant of strong binding affinity is the hydrogen bond from N51 of piperazine ring, which can be found only in Abl1 kinase. Our results suggested how to improve the binding affinity between Gleevec and p38-MAPK based on the distances among active site residues from multiple crystal structures.
King Mongkut's University of Technology North Bangkok. Central Library
Address:
BANGKOK
Email:
library@kmutnb.ac.th
Created:
2019
Modified:
2019-08-30
Issued:
2019-08-30
บทความ/Article
application/pdf
BibliograpyCitation :
In Chemical Society of Thailand under the Patronage of Professor Dr. HRH Princess Chulabhorn. Pure and Applied Chemistry International Conference 2019 (PACCON 2019) (CB16-19). Bangkok : Mahidol University
eng
©copyrights King Mongkut's University of Technology North Bangkok
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ใช้เวลา
0.023637 วินาที
Natsasion Srithiowat
| Title | Contributor | Type |
|---|---|---|
| Structure-based drug design approaches to improve Gleevec as promiscuous drug
มหาวิทยาลัยเทคโนโลยีพระจอมเกล้าพระนครเหนือ Natsasion Srithiowat;Duangrudee Tanramluk | บทความ/Article |
Duangrudee Tanramluk
| Title | Contributor | Type |
|---|---|---|
| Crystal structure of plasmodium falciparum dihydrofolate reductase-thymidylate synthase in complex with trimethoprim
มหาวิทยาลัยมหิดล Duangrudee Tanramluk | Jirundon Yuvaniyama | วิทยานิพนธ์/Thesis |
| Structure-based drug design approaches to improve Gleevec as promiscuous drug
มหาวิทยาลัยเทคโนโลยีพระจอมเกล้าพระนครเหนือ Natsasion Srithiowat;Duangrudee Tanramluk | บทความ/Article |