Fragment-Based Drug Discovery: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older editNewer edit →
No edit summary
No edit summary
Line 26: Line 26:
===== ABT-737: ligand screening =====
===== ABT-737: ligand screening =====


<scene name='Sandbox_reserved_394/Compound_1/12'>Two fragments</scene> were found to have moderate affinity for Bcl-xl. <scene name='Sandbox_reserved_394/Compound_1/9'>Compound 1</scene> is a fluorobiphenylcarboxylic acid. It occupies <scene name='Sandbox_reserved_394/Binding_site_1/2'>binding site 1</scene> of Bcl-xl which consists of Phe 101, Tyr 105, Ala 108, Phe 109, Leu 136, Gly 142, Arg 143, and Ala 146. The fluorobiphenyl system of compound 1 is very hydrophobic and therefore, these residues form a <scene name='Sandbox_reserved_394/Compound_1/4'>"hydrophobic pocket"</scene> around the system. There is also one hydrophilic interaction involved in this complex. The <scene name='Sandbox_reserved_394/Compound_1/5'>carboxylic acid portion of compound 1 binds near Gly 142</scene> of Bcl-xl. This is not a strong interaction but is significant because it can be modified to form a much stronger bond.
<scene name='Sandbox_reserved_394/Compound_1/12'>Two fragments</scene> were found to have moderate affinity for Bcl-xl. <scene name='Sandbox_reserved_394/Compound_1/9'>Compound 1</scene> is a fluorobiphenylcarboxylic acid. It occupies <scene name='Sandbox_reserved_394/Binding_site_1/4'>binding site 1</scene> of Bcl-xl which consists of Phe 101, Tyr 105, Ala 108, Phe 109, Leu 136, Gly 142, Arg 143, and Ala 146. The fluorobiphenyl system of compound 1 is very hydrophobic and therefore, these residues form a <scene name='Sandbox_reserved_394/Compound_1/4'>"hydrophobic pocket"</scene> around the system. There is also one hydrophilic interaction involved in this complex. The <scene name='Sandbox_reserved_394/Compound_1/5'>carboxylic acid portion of compound 1 binds near Gly 142</scene> of Bcl-xl. This is not a strong interaction but is significant because it can be modified to form a much stronger bond.


<scene name='Sandbox_reserved_394/Compound_1/3'>Compound 2</scene> is a napthalene-based alcohol which occupies <scene name='Sandbox_reserved_394/Binding_site_2/4'>binding site 2</scene>. This particular fragment also is involved with hydrophobic interactions with Bcl-xl, although they are not as strong as in the case of compound 1. This binding site includes Ala 97, Glu 100, Phe 101, Val 145, and Tyr 199.
<scene name='Sandbox_reserved_394/Compound_1/3'>Compound 2</scene> is a napthalene-based alcohol which occupies <scene name='Sandbox_reserved_394/Binding_site_2/4'>binding site 2</scene>. This particular fragment also is involved with hydrophobic interactions with Bcl-xl, although they are not as strong as in the case of compound 1. This binding site includes Ala 97, Glu 100, Phe 101, Val 145, and Tyr 199.
Retrieved from "https://proteopedia.org/Fragment-Based_Drug_Discovery"