Heparin/heparan sulfate (H/HS)-like oligosacaccharides (S-OligoS) were studied in vitro to elucidate their multifunctional modulation of protein and cell membrane function: 1) Struc/fxn of heparin substitute, SP54, which like H/HS inhibits infectiousness of HIV-1 in vitro, was continued. Capacities of 17 newly purified MW components (Cpts) of SP54 to inhibit HIV-1-induced syncytia formation and cytotoxicity confirmed that Cpts of greater than 5000 MWapp and a specific approximately octaS (approximately 1.8% of SP54) both were highly active inhibitors of cytotoxicity [EC50=200 ng/ml and 580 ng/ml], while high-potency inhibition of syncytium formation resided solely in Cpts greater than 5000 MWapp [EC50 = 200-300 ng/ml]. This first demonstration of structural specificity and different structural requirements for the inhibition of HIV-1 """"""""cell entry"""""""" and cell fusion by S-oligoS offers potential adjunct to AIDS therapy and understanding of viral cell reactions. 2) In vitro inhibition by sulfated beta-cyclodextrin of growth of Kaposi Sarcoma cell lines derived from AIDS patients [EC50 -15 ug/ml] also exhibited differential activity: 7 sugars and an av of 1S/sugar was required, with highest potency (5-10-fold enriched) in Cpt(s) having less than max av S. 3) Modulation of basic fibroblast growth factor (bFGF) by H and suramin (S) was demonstrated by CD and fluorescence spectroscopy to involve direct conformational alteration of its receptor-binding region. S was bound within 1 nm of the sole bFGF tryptophan.
