Sandbox Reserved 1474: Difference between revisions
No edit summary |
No edit summary |
||
| (4 intermediate revisions by the same user not shown) | |||
| Line 94: | Line 94: | ||
===Human-mouse chimeric monoclonal antibody(mAb) Ch-mAb7F9=== | ===Human-mouse chimeric monoclonal antibody(mAb) Ch-mAb7F9=== | ||
IgG mAbs are typically chimeric, humanized, or fully human proteins. The longest t1/2lamdaz values are usually achieved when the antibody does not bind to tissue sites and is not prematurely cleared due to antigenicity. | IgG mAbs are typically chimeric, humanized, or fully human proteins. The longest t1/2lamdaz values are usually achieved when the antibody does not bind to tissue sites and is not prematurely cleared due to antigenicity<ref name="Preclinical characterization of an anti-methamphetamine monoclonal antibody for human use"/> | ||
Ch-mAb7F9, a chimeric mAb is produced as a treatment medication for METH abuse based on the murine anti-METH mAb7F9. It is created by preserving mAb7f9 variable region with human IgG2 constant domains to minimize the risk of effector function. In vitro, it is shown only binds to (+)METH (KD=6.9nM), (+)AMP(KI = 350 nM), (+)MDMA(kI=6.7nM). | . | ||
Ch-mAb7F9, a chimeric mAb is produced as a treatment medication for METH abuse based on the murine anti-METH mAb7F9<ref name="Pharmacological effects of two anti-methamphetamine monoclonal antibodies"/>. It is created by preserving mAb7f9 variable region with human IgG2 constant domains<ref name="Preclinical characterization of an anti-methamphetamine monoclonal antibody for human use"/> to minimize the risk of effector function. In vitro, it is shown only binds to (+)METH (KD=6.9nM)<ref name="Preclinical characterization of an anti-methamphetamine monoclonal antibody for human use"/> | |||
, (+)AMP(KI = 350 nM)<ref name="Preclinical characterization of an anti-methamphetamine monoclonal antibody for human use"/> | |||
, (+)MDMA(kI=6.7nM)<ref name="Preclinical characterization of an anti-methamphetamine monoclonal antibody for human use"/> | |||
. | |||
| Line 210: | Line 214: | ||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4lar FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lar OCA], [http://pdbe.org/4lar PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4lar RCSB], [http://www.ebi.ac.uk/pdbsum/4lar PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4lar ProSAT]</span> | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4lar FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lar OCA], [http://pdbe.org/4lar PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4lar RCSB], [http://www.ebi.ac.uk/pdbsum/4lar PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4lar ProSAT]</span> | ||
}} | }} | ||
{{ STRUCTURE | {{ STRUCTURE | ||
|PDB=3gkz | |PDB=3gkz | ||
| Line 224: | Line 225: | ||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4lar FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lar OCA], [http://pdbe.org/4lar PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4lar RCSB], [http://www.ebi.ac.uk/pdbsum/4lar PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4lar ProSAT]</span> | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4lar FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lar OCA], [http://pdbe.org/4lar PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4lar RCSB], [http://www.ebi.ac.uk/pdbsum/4lar PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4lar ProSAT]</span> | ||
}} | }} | ||
===Aromatic-Aromatic Interaction: A Mechanism of Protein Structure Stabilization=== | ===Aromatic-Aromatic Interaction: A Mechanism of Protein Structure Stabilization=== | ||
The entrance of the binding pocket is lined with seven amino residues, one residue from each of them H1, H2, and H3 loops, 3 from the L3 loop, one from the beta-strand-3c of the heavy chain. These aromatic residues form a hydrophobic barrel around the aromatic portion of METH. | The entrance of the binding pocket is lined with seven amino residues, one residue from each of them H1, H2, and H3 loops, 3 from the L3 loop, one from the beta-strand-3c of the heavy chain. These aromatic residues form a hydrophobic barrel around the aromatic portion of METH<ref name="Crystal structures of a therapeutic single chain antibody in complex with two drugs of abuse-methamphetamine and 3,4-methylenedioxymethamphetamine"/>. | ||
===Hydrophilic interactions of METH=== | ===Hydrophilic interactions of METH=== | ||
The protonated secondary amine of METH anchors the ligand deep in the pocket. There is a salt bridge between the cationic nitrogen of METH and the carboxyl oxygen of Glutamate. In addition, the cationic nitrogen forms a hydrogen bond to Hisdine of the light chain<ref name="Crystal structures of a therapeutic single chain antibody in complex with two drugs of abuse-methamphetamine and 3,4-methylenedioxymethamphetamine"/>. | |||
===Water molecules in the binding cavity=== | ===Water molecules in the binding cavity=== | ||
two water molecules are in the pocket stablized by hydrogen bonding bewteen and with the side chain residues<ref name="Crystal structures of a therapeutic single chain antibody in complex with two drugs of abuse-methamphetamine and 3,4-methylenedioxymethamphetamine"/>. | |||
{{ STRUCTURE | {{ STRUCTURE | ||
| Line 253: | Line 247: | ||
}} | }} | ||