Erfahrungen mit »ultrahohen« Cyclophosphamid-Dosen an 42 Kranken mit soliden des lymphoretikulären Tumoren

Abstract

Erfahrungen mit »ultrahohen« Cyclophosphamid-Dosen an 42 Kranken mit soliden und lymphoretikulären Tumoren Das seit 1958 im Handel befindliche Alkylans Cyclophosphamid zählt zu den am besten wirksamen Zytostatika bei relativ geringen Nebenwirkungen. Man hat es früher überwiegend protrahiert in täglichen Dosen von 100-300 mg gegeben, ist aber seit den Arbeiten von Druckrey und Mitarbeitern (20) in zunehmendem Maß auf die »Stoßtherapie« mit Dosen von 15-40 mg/kg in ein-bis dreiwö-

Epidermin: sequencing of a heterodet tetracyclic 21‐peptide amide antibiotic

“…Again the mlz of the unknown residue R was found to be 44. It should be noted here that all molecular masses as experimentally determined by FD and FAB-MS were higher by 2 than expected if the peptides were N-terminally blocked by the pyruvyl group: P2, P21, P22, P21 (14)(15)(16)(17)(18)(19)(20), and P22-0. This may be explained by a reduction of the a-carbonylgroup of the 2-oxobutyryl group within the matrix applied for the MS samples.…”

“…After 24 h at 37"C, acetic acid was added to pH 4 and lyophilized. Two products were detected: the more Iipophilic P21 (14)(15)(16)(17)(18)(19)(20) Cleavage of P22 with a-chymotrypsin. Following the procedure described for the cleavage of P21, one ninhydrin-positive product P22-0 was obtained from P22, which contained the intact sulfur bridge of the meso-Lan residue.…”

“…Even the desulfurized fragments P21 and P21 (14)(15)(16)(17)(18)(19)(20) were not accessible to common sequencing procedures because of their blocked N-and C-termini. Unfortunately, we did not succeed in attempts for the oxidative removal of the 2-oxoacyl group as described by McGregor and Carpenter [13].…”

“…Only a-chymotrypsin affected complete conversion after 24 h, whereas the reaction also observed with thermolysin was due to an a-chymotryptic impurity. The analysis of preparative amounts of the chymotryptic N-blocked product P21 (14)(15)(16)(17)(18)(19)(20) indicated the lack o f one L-alanine residue, which had to originate from meso-Lan. The second chymotryptic product was the ~-Ala'l-R ninhydrin-positive fragment L-Ala" -R, which will be discussed below.…”

“…Carboxypeptidase A cleaved tyrosine as C-terminal amino acid from fragment P21 (14)(15)(16)(17)(18)(19)(20). Therefore the desulfurized fragment P21 had the composition H3C-CH2-COCO-(2 D-Ala,Gly,L-Phe,L-Asn)-L-Tyr20-L-Ala2'-R. Further information was obtained after chymotryptic cleavage of P22 with an intact meso-Lan ring system.…”