A LIPOPHILIC DERIVATIVE OF NEOCARZINOSTATIN A Polymer Conjugation of an Antitumor Protein Antibiotic*

Abstract

A lipophilic derivative of neocarzinostatin (NCS), an antitumor antibiotic, was prepared by reaction with a synthetic water-soluble polymer, [(styrene)_1˜3-(maleic acid_4˜7/anhydride₁)]. The reaction was carried out at pH 8.6 for 3 h and aimed at modifying the two nonessential aming (of Ala-1, ε-amino of Lys-20). The NCS-polystyrene (SMANCS was a column of Sephadex G-100 in 0.05 M ammonium bic and the main product was obtained as a single peak. The elemental and showed an increased C and a decreased N content. U.v. and i.r. absorption ectra for SMANCS showed the presence of styrene. SDS-acrylamide gel electrophoresis at pH 8.5 and the decreased N content suggested a molecular high of about 25 000, Indicating the numbers of polymers conjugated to be six units, two of which were found attached to the two amino groups. SMANCS was solution in organic solvents, in contrast to NCS, and in water. SMANCS increased chemical and biological stability and appeared molicular in vitro biological activity.