Similarity based virtual screening: a tool for targeted library design.
High throughput screening drug discovery utilizes large and expensive compound libraries. As an alternative, a smaller targeted library can be constructed with the aid of the 3D structure of the target molecule. We used the X-ray crystal structure of a protein homologous to the selected target in creation of a small focused library and evaluated inhibition potential of this library against Chlamydia pneumoniae, a common pathogen recently linked to atherosclerosis and risk of myocardial infarction.
Alvesalo
Joni K O
JK
Drug Discovery and Technology Development Center (DDTC), Faculty of Pharmacy, P.O. Box 56, FIN-00014 University of Helsinki, Finland.
Siiskonen
Antti
A
Vainio
Mikko J
MJ
Tammela
Päivi S M
PS
Vuorela
Pia M
PM
D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001412:Bacillus subtilis / Q000201:enzymology; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016993:Chlamydophila pneumoniae / Q000187:drug effects* / Q000201:enzymology; D018360:Crystallography, X-Ray; D016208:Databases, Factual; D015195:Drug Design; D006801:Humans; D008024:Ligands; D008780:Methyltransferases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D008958:Models, Molecular; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011487:Protein Conformation; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D000081:Acetamides; D000900:Anti-Bacterial Agents; D001549:Benzamides; D001562:Benzimidazoles; D008024:Ligands; D010069:Oxadiazoles; D011725:Pyridines; D008780:Methyltransferases; C047346:16S rRNA (adenine(1518)-N(6)-adenine(1519)-N(6))-dimethyltransferase