Cell biology, chemogenomics and chemoproteomics - application to drug discovery

被引:4
作者
Gagna, Claude E. [1 ,2 ]
Lambert, W. Clark [1 ]
机构
[1] Univ Med & Dent New Jersey, Dept Pathol & Lab Med, Newark, NJ 07103 USA
[2] New York Coll Osteopath Med, New York Inst Technol, Dept Life Sci, Sch Hlth Profess Behav & Life Sci, Old Westbury, NY 11568 USA
关键词
alternative DNA; cell biology; chemical genomics; chemogenomics; chemoproteomics; chemical proteomics; DNA microarrays; multi-stranded DNA; tissue microarrays; transitional structural chemogenomics; transitional structural chemical genomics; transitional structural chemoproteomics; transitional structural chemical proteomics;
D O I
10.1517/17460441.2.3.381
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Cell biology has added immensely to the understanding of basic biologic concepts. However, scientists need to use cell biology more in the proteomic genomic revolution. The authors have developed two novel techniques: transitional structural chemogenomics (TSCg) and transitional structural chemoproteomics (TSCp). TSCg is used to regulate gene expression by using ultrasensitive small-molecule drugs that target nucleic acids. By using chemicals to target transitional changes in the helical conformations of single-stranded (ss) and double-stranded (ds) DNA (e.g., B- to Z-DNA) and RNA (e.g., A- to Z-RNA), gene expression can be regulated (i.e., turning genes 'on/off' and variably controlling them). Alternative types of ds- and ssDNA and RNA (e.g., cruciform DNA) and other multistranded nucleic acids (e.g., triplex-DNA) are also targeted by this method. The authors' second technique, TSCp, targets a protein before, during or after post-translational modifications, which alters the protein's structure and function. These novel methods represent the next step in the evolution of chemical genomics and chemical proteomics. In addition, a novel multi-stranded (alternative) DNA, RNA and plasmid microarray has been developed that allows for the immobilization of intact, non-denatured dsDNA, alternative (i.e., exotic) and other multiple-stranded nucleic acids. This represents the next generation of nucleic acid microarrays, which will aid in the characterization of nucleic acids, studying the ageing process and improving the drug discovery process. The authors discuss how cell biology can be used to enhance genomics and proteomics. Cell biology will play a greater role during the postgenomic age and will help to enhance the omics/omes and drug discovery. It is the authors' hope that these novel approaches can be used together with cellular biologic techniques to make major contributions towards understanding and manipulating different genomes.
引用
收藏
页码:381 / 401
页数:21
相关论文
共 95 条
[1]  
Alberts B., 2002, Molecular Biology of The Cell, V4th
[2]  
Arosarena Oneida, 2005, Curr Opin Otolaryngol Head Neck Surg, V13, P233, DOI 10.1097/01.moo.0000170526.51393.c5
[3]   Strategies to identify disease genes [J].
Ashton, GHS ;
McGrath, JA ;
South, AP .
DRUGS OF TODAY, 2002, 38 (04) :235-244
[4]   The completed human genome: implications for chemical biology [J].
Austin, CP .
CURRENT OPINION IN CHEMICAL BIOLOGY, 2003, 7 (04) :511-515
[5]   4Pi-confocal microscopy of live cells [J].
Bahlmann, K ;
Jakobs, S ;
Hell, SW .
ULTRAMICROSCOPY, 2001, 87 (03) :155-164
[6]   Pharmacogenomics - it's not just pharmacogenetics [J].
Bailey, DS ;
Bondar, A ;
Furness, LM .
CURRENT OPINION IN BIOTECHNOLOGY, 1998, 9 (06) :595-601
[7]   Chemoproteomics as a basis for post-genomic drug discovery [J].
Beroza, P ;
Villar, HO ;
Wick, MM ;
Martin, GR .
DRUG DISCOVERY TODAY, 2002, 7 (15) :807-814
[8]   Selective staining of proteins with hydrophobic surface sites on a native electrophoretic gel [J].
Bertsch, M ;
Kassner, RJ .
JOURNAL OF PROTEOME RESEARCH, 2003, 2 (05) :469-475
[9]   Chemoinformatics - predicting the physicochemical properties of 'drug-like' molecules [J].
Blake, JF .
CURRENT OPINION IN BIOTECHNOLOGY, 2000, 11 (01) :104-107
[10]   DNA structural transitions within the PKD1 gene [J].
Blaszak, RT ;
Potaman, V ;
Sinden, RR ;
Bissler, JJ .
NUCLEIC ACIDS RESEARCH, 1999, 27 (13) :2610-2617