MITOGENIC ACTIVITY AND THE INDUCTION OF TUMOR-NECROSIS-FACTOR BY LIPOPEPTIDE ANALOGS OF THE N-TERMINAL PART OF LIPOPROTEIN IN THE OUTER-MEMBRANE OF ESCHERICHIA-COLI

Mitogenicity and the production of tumor necrosis factor (TNF) by a ch emically synthesized lipotetrapeptide analog (KAB-8), y)-2R-propyl]-N- [(2,2,2)-trichloro-ethoxycarbonyl: Troc -(R)-cysteinyl-(S)-seryl-(S)-s eryl-(S)-asparagine, the amino acid sequence of which corresponds to t hat of the lipopeptide part of lipoprotein in Escherichia coli, and se veral derivatives (KAB-30-41), which possessed the altered glycerocyst eine moiety, were examined. A 1-cysteinyl glycerol skeleton-type compo und (KAB-8), a propane-type compound (KAB-31), a homoglycerol-type (KA B-39 and 40) and a 2-cysteinyl glycerol-type (KAB-41) exhibited mitoge nic activity on splenocytes from C3H/He mice at various concentrations ranging from 0.4 to 100 mug/ml. However, propane-type compounds, exce pt KAB-31, and ethane-type compounds showed lower mitogenic activity t han other types of compounds. Compounds KAB-8, 31, 40 and 41 induced t he production of TNF in peritoneal exudated macrophages from C3H/He mi ce at concentrations of 25 and 50 mug/ml. The results indicate that th e structural differences of the glycerol moiety in the synthetic lipop eptides affect the potency of its biological activities.