Bleomycins biological activity

The overall strategy is shown in Figure 2. In the first step, nonradio-active cobalt (II) is bound to bleomycin A2 and air-oxidized to form the stable cobalt (III)-bleomycin A2 complex. The dimethyl(y-aminopropyl)-sulfonium group at the right side of the structure is unique to bleomycin A2 the other bleomycins have quite different terminal amine residues. Since the biological transport properties of all of the bleomycins are similar (17), the structure of the terminal amine residue appears to have relatively little influence on transport into cancer cells therefore this residue is a promising site for chemical modification. 

Thus, COET is important as the oxygen-activation process not only in heme enzymes but also in other biological systems such as the bleomycin-Fe(II)-02 system. 

Methods for synthesizing anisomycin and pentenomycin, ° and the chemistry and biological transformations of bleomycin and phleomycin have been reviewed.D-Ribo-furanosyl and -pyranosyl derivatives of iV-methyl-iV-nitroso-urea have been prepared as analogues of streptozotocin [2-deoxy-2-(JV-methyl-A -nitrosoureido)-D-glucose] they were reported to be more active against LI 210 leukaemia in mice and less toxic than the parent antibiotic. Likewise N- 2-chloroethyl)-iV-nitrosoureido derivatives of cyclopentane tetrols (35) and cyclohexane tetrols (36) have been synthesized for comparison with streptozotocin. ... 

From a biological perspective the bleomycin (BLM) family of antibiotics that are used widely in chemotherapy, have stimulated considerable effort in understanding oxygen activated iron complexes. In particular iron bleomycin reacts with oxygen to form the so-called purple species, which exhibits an absorption band around 600 nm that is now known to be characteristic of the Fe -OOH species. In the case of Fe-BLM the active intermediate has been identified spectroscopically as a low-spin Fe -hydroperoxide. Several structural mimics of the metastable purple Fe -OOH species have been prepared, in particular complexes with neutral pentadentate ligands e.g., l,l-di(pyiidin-2-yl)-N,N-bis(pyridin-2-ylmethyl)-ethanamine (N4Py) Resonance Raman spectroscopy has proven... 

Williams, J.H., Chen, M, Drew, J., Panigan, E. and Ilosseini, S. (1988) Modulation of rat granulocyte traffic by a surface active agent in vitro and bleomycin injury. Proceedings of the Society for Experimental Biology and Medicine, 188, 461-470. 

The reduction potential of Fe(III)BLM is +129 12 mV (vs. NHE) and thus the Fe(II) form can be easily regenerated under biological conditions by reducing agents such as GSH or Oj [73]. The chemistry of activated bleomycin has been recently reviewed [111]. 

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