浏览： 日期：2019-06-15
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1, Introduction |
2 |
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2, Ligand - Galantamine (GNT) |
2 |
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2.1, Structural description |
2 |
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2.2, MM2 energy minimization |
3 |
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2.3, Drug likeness assessment |
3 |
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3, Acetylcholinesterase(AChE) (PDB 1W6R) |
4 |
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3.1, Primary structural information |
4 |
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3.2, Secondary Structural Information |
5 |
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3.3 Three Dimensional structure |
6 |
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4, Protein-ligand interactions |
9 |
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4.1, General view of interactions with in GNT-AchE complex |
9 |
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4.2,Comments on the fit of ligand into binding site |
12 |
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5, Conclusion |
12 |
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6, References |
12 |
Galantamine (GNT) (2D structure showed in Fig 1) is a tertiary alkaloid extracted from several species of Amarylidacae, discovered more than 52 years ago, it has been tested in various neurological applications and has been proved to be a potent reversible inhibitor to AChE. Details of this compound are provided from different perspectives in this part.
Fig 1: 2D structure of GNT
Table 1: Basic chemistry information of GNT (information gathered form ChemOffice 2004)
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Common name |
Galantamine (GNT) |
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Chemical Formula |
C17H21NO3 |
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CAS number |
357-70-0 |
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IUPAC Name |
(4aS,6R,8aS)- 5,6,9,10,11,12- hexahydro- 3-methoxy- 11-methyl- 4aH- 1benzofuro3a,3,2-ef2benzazepin- 6-ol |
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Smiles string |
HC@12CC@@H(O)C=CC@11CCN(C)CC3=CC=C(OC)C(O2)=C13 |
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Chiral Atom Count |
3 |
Chiral Atoms |
C3 C41 C42 |
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Number of rings |
4 |
Bond Count |
45 |
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Log P |
1.2 |
Aromatic Bond |
6 |
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MR |
84.22cm3/mol |
CMR |
7.9778 |
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Molar Refractivity |
78.20 cm3/mol |
Normal Boiling Point |
817.71 K |
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Henry's Constant (H) |
10.37 |
Freezing Point |
542.75 K |
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Melting point |
578.64 K |
Critical temp |
855.94 K |
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Critical Pressure |
23.35 bar |
Critical Volume |
803.50 cm3/mol |
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Gibbs Energy |
151.32 kJ/mol |
Heat of Formation |
-255.66kJ/mol |
In order to get a more stable and low-energy conformation, which is more likely to present in interaction between GNT and target protein, we run a MM2 energy minimization and output shows that orientation of functional groups in GNT change significantly, which can be observed very obviously in Figure 2.
Figure 2, Sequence of pictures showing 3D structure and Connolly surface of GNT before (A, C) and after (B, D) MM2 energy minimization, GNT is rendered as a ball-and-stick model and the surface is rendered in transparent solid model. This view is generated by Chem3D Ultra.
