new solid phase synthesis of distamycin analogues新的distamycin固相合成的类似物.pdfVIP

Molecules 2011, 16, 3066-3076; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article New Solid Phase Synthesis of Distamycin Analogues Drozdowska Danuta Department of Organic Chemistry, Medical University, Mickiewicza 2A Str., 15-222 Białystok, Poland; E-Mail: danuta.drozdowska@.pl; Tel.: +48 85 7485684; Fax: +48 85 7485416 Received: 28 February 2011; in revised form: 31 March 2011 / Accepted: 2 April 2011 / Published: 11 April 2011 Abstract: A novel and straightforward solid phase synthesis of distamycin analogues containing benzene units has been developed. Keywords: combinatorial chemistry; solid phase synthesis, distamycin analogues 1. Introduction Distamycin A (Figure 1) is natural antibiotic with anticancer activity. This compound is one of the most extensively studied members of class of molecules that can bind reversibly in the minor groove of duplex DNA, by hydrogen bonds, van der Waals contacts and electrostatic interactions, with high specificity for regions containing A-T base pairs [1].The molecule of distamycin is oligopeptide constructed with 4-amino-1-methylpyrrole acid moieties and strong basic side chains, possessing isohelical shape to minor groove DNA [2, 3]. Figure 1. Structure of distamycin A. NH NH O NH2 HN