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Structural and conformational features relevant to the anti‐tumor activity of calicheamicin γ 1 I
Author(s) -
Ellestad George A.
Publication year - 2011
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.20990
Subject(s) - calicheamicin , chemistry , enediyne , cleavage (geology) , circular dichroism , dna , stereochemistry , molecular mechanics , biophysics , nuclear magnetic resonance spectroscopy , combinatorial chemistry , biochemistry , molecular dynamics , computational chemistry , antibody , geotechnical engineering , fracture (geology) , engineering , immunology , biology
The structural and conformational features of the potent 10‐membered enediyne‐containing calicheamicin γ 1 Ithat account for its remarkable DNA site‐specific binding and cleavage are reviewed. A variety of spectroscopic and biophysical techniques were used to gain insight into the binding and stereospecific DNA cleavage of this potent antitumor agent. These include gel‐shift cleavage assays, atom transfer NMR experiments, drug‐DNA conformational studies, circular dichroism, and capillary electrophoresis . Computational descriptions are described for the DNA binding and cleavage of calicheamicin and its activated transient intermediates based on density functional and molecular mechanics calculations. In addition , the structure and clinical utility of calicheamicin immunoconjugates for antibody‐targeted chemotherapy is presented. Chirality, 2011. © 2011 Wiley‐Liss, Inc.