CIRCULAR-DICHROISM EVIDENCE OF THE LEFT-HANDED CONFORMATION ADOPTED BY CYCLOPROPYLPYRROLOINDOLE ANTITUMOR ANTIBIOTICS IN SOLUTION

The purpose of this work was to determine the conformation adopted in solution by adozelesin, carzelesin, and their derivatives obtained und er basic or acidic conditions. Circular dichroism in the 270-330 nm wa velengths region was studied. In solution adozelesin can adopt two dif ferent conformations: a left-handed one which is thermodynamically fav oured at low temperature and is mainly present at room temperature, an d a right-handed one which is observed either at high temperature or a t room temperature in the presence of DNA. This was ascertained by the presence of circular dichroism signals of the couplet type. The activ e form of carzelesin, i.e., U-76074, also exhibited a left-handed conf ormation in solution. Carzelesin and the derivatives obtained under ac idic conditions that lack the cyclopropyl ring, and cyclopropylpyrrolo indale, obtained under basic conditions,cannot adopt such a conformati on. (C) 1997 Wiley-Liss, Inc.