Vol. 108, No. 1, 1982 8lOCHEMlCAL AND BIOPHYSICAL RESEARCH COMMUNlCATlONS September 16, 1982 Pages 315-321 AMINO ACID SEQUENCE HOMOLOGIES IN ALFA-SARCIN, RESTRICTOCIN AND MITOGILLIN R. RODRIGUEZ*, C. LOPEZ-OTIN+, D. BARBER+,J.L. FERNANDEZ-LUNA+ G. GONZALEZ*, and E. MENDEZ+l +Servicio de Endocrinologia, Centro Ramon y Cajal Carretera de Colmenar Km 9, 100, Madrid, Spain l Departamento de Bioquimica, Facultad de Ciencias Universidad Complutense, Madrid, Spain Received July 29, 1982 The NHZ-terminal amino acid sequence of the three anti-tumor proteins, alfa-sarcin, mitogillin and restrictocine, has been determined for 20 cycles by automated sequencing procedure. A high degree of sequence homology was observed in this region of the molecule. In addition, extensive sequence homology, ranging from 65 to 100% was found in three other carboxymethylcysteine- containing peptides isolated and sequenced from each molecule. INTRODUCTION Alfa-sarcin, restrictocin and mitogillin are three antitumor agents produced by two different Aspergillus strains (l-3). These three molecules have been characterized as basic polypeptide chains with molecular weights of about 16,000 (4-8). They inactivate the eukaryotic 60 S ribosomal subunit by cleavage of the large RNA (4-6). These proteins are also powerful inhibitors "in viva" of protein synthesis in picornavirus infected cells, since they are able to penetrate the cell only when the latter is first infected with picornavirus (8). The antibodies for alfa-sarcin can prevent the action of the toxin on the ribosomes. Alfa-sarcin antiserum cross-reacts with the other two toxins from Aspergillus and is also able to prevent their effects on the ribosome (6). We now report partial structural characterization of these polypeptides and show that they exhibit extensive sequence homologies in the peptides around the disulfide bonds. 1. To whom correspondence should be addressed. 0006-291X/82/170315-07$01.00/0 315 Copyright 0 1982 by Academic Press, Inc. AN rights of reproduction in any form reserved.