Forward chemical genetics: library scaffold design.
With the unraveling of the entire human genome, it has become imperative to understand the function of the gene products, proteins. Within the past several years, chemical genetics has gained recognition as a powerful approach to study protein function by using small molecules as gene knock-out or knock-in mimics. Forward chemical genetics is a three-step process; the design and synthesis of a small molecule library represents the first step followed secondly by the search for novel phenotypes and then by isolation and identification of target protein(s). This review will focus on the first step, the design of the scaffold for small molecule libraries. It will also examine the connection between the choice of a scaffold and the propensity of that library to demonstrate enhanced biological activity when tested in certain cellular systems.
Khersonsky
Sonya M
SM
Department of Chemistry, New York University, New York, New York 10003, USA.
Chang
Young-Tae
YT
D000818:Animals; D015195:Drug Design; D006801:Humans; D040901:Proteomics; D011687:Purines / Q000737:chemistry; D021281:Quantitative Structure-Activity Relationship; D013110:Sphingosine / Q000737:chemistry; D013343:Styrenes / Q000737:chemistry; D014227:Triazines / Q000737:chemistry
D011687:Purines; D013343:Styrenes; D014227:Triazines; D013110:Sphingosine