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A New and Unusual Pathway for the Reaction of Neocarzinostatin Chromophore with Thiols. Revised Structure of the Protein-Directed Thiol Adduct

Myers, Andrew G. and Arvedson, Stephen P. and Lee, Robert W. (1996) A New and Unusual Pathway for the Reaction of Neocarzinostatin Chromophore with Thiols. Revised Structure of the Protein-Directed Thiol Adduct. Journal of the American Chemical Society, 118 (19). pp. 4725-4726. ISSN 0002-7863. https://resolver.caltech.edu/CaltechAUTHORS:20170905-105552868

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Abstract

Neocarzinostatin (holo-NCS) is an antitumor antibiotic comprising a nonprotein chromophore component (1) and a 113- amino acid carrier protein (apo-NCS). Goldberg and coworkers first demonstrated that the reaction of the isolated chromophore (1) with thiols in the presence of double-stranded DNA leads to DNA cleavage by a free-radical mechanism. The pathway shown in Scheme 1 was later proposed to account for this activity, a proposal that is now supported by a considerable body of evidence. In 1992, Saito and co-workers showed that the reaction of holo-NCS with small thiols, such as β-mercaptoethanol (BME), takes a different course, to form a product that is formally a 1:1:1 adduct of thiol, 1, and water. Structure 2 was proposed for this adduct, along with the mechanistic pathway shown in Scheme 2. Complicating the analysis was the fact that 2 was an inseparable mixture of two components, present in equal parts.


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https://doi.org/10.1021/ja960335+DOIArticle
http://pubs.acs.org/doi/abs/10.1021/ja960335%2BPublisherArticle
http://pubs.acs.org/doi/suppl/10.1021/ja960335%2B/suppl_file/ja4725.htmlPublisherSupporting Information
Additional Information:© 1996 American Chemical Society. Received February 1, 1996. Publication Date (Web): May 15, 1996. We are grateful to Prof. Dennis A. Dougherty and Dr. James L. Gleason for insightful discussions and Dr. Scott B. Cohen for technical assistance in the early stages of this project. This work was generously supported by the NIH. S.P.A. gratefully acknowledges an NSF Pre-Doctoral Fellowship.
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Issue or Number:19
Record Number:CaltechAUTHORS:20170905-105552868
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170905-105552868
Official Citation:A New and Unusual Pathway for the Reaction of Neocarzinostatin Chromophore with Thiols. Revised Structure of the Protein-Directed Thiol Adduct. Andrew G. Myers, Stephen P. Arvedson, and, and Robert W. Lee. Journal of the American Chemical Society 1996 118 (19), 4725-4726 DOI: 10.1021/ja960335+
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ID Code:81135
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:05 Sep 2017 19:29
Last Modified:03 Oct 2019 18:39

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