DK690587A - TETRAPEPTIME, ITS MANUFACTURING AND USE - Google Patents

Abstract

The tetrapeptide of the formula Ser-Asp-Lys-Pro-OH and its derivatives which have resulted by means of substitution by one or more identical or different groups which are normally employed in peptide chemistry for biological use, and pharmaceutically acceptable salts thereof, in particular the tetrapeptide of the formula Ser-(N-Ac)-Asp-Lys-Pro-OH which can be prepared by a process which comprises the following steps: grinding the starting material, if necessary together with delipidization, suspending the resulting product in a buffer at a pH in the vicinity of 7 and in the presence of a silver-containing reducing reagent, in particular dithioerythritol or, preferably, mercaptoethanol, centrifuging the homogenate at approx. 15,000 g for at least 1 hour, subjecting the above liquid to ultrafiltration on a membrane having a cut-off limit in the vicinity of 10,000 daltons, chromatographing the resulting ultrafiltrate on a molecular sieve of the polyacrylamide gel type, with elution taking place using a dilute acetic acid solution, fractionating the collected active fraction on a reverse phase support of silicon dioxide grafted with aliphatic groups, in particular C18 groups, with this step preferably being repeated at least once, and subjecting the resulting active fraction to high pressure liquid chromatography on a reverse phase column of silicon dioxide grafted with aliphatic groups, in particular C18 groups, in order to produce a uniform active fraction, or can be prepared by means of peptide synthesis, is particularly useful for protecting bone marrow when using chemotherapy to treat cancer.