Heparin/heparan sulfate and heparin-mimetic sulfated oligosaccharides (S- oligoS) are studies in-vitro to elucidate the structural basis of their modulations of protein and cell membrane function: I) In one such structure/function study, we have proposed that S-oligoS play a role in mechanisms underlying destruction of the immune system by human immunodeficiency virus-I (HIV). The S-oligoS inhibit infectivity if HIV in vitro. By purifying components (Cps) of SP54 (a mixture of fragments of sulfated xylan) ranging from 2000 to 25000 in MWtapp, we demonstrated that inhibition of HIV-induced cytotoxicity (CT) and syncytium-formation (SF) in CD4-cells was indeed governed by a structural specificity. In addition, a specific low MWt Cp exhibited high anti-CT potency (CpX) (Z01 MH 02593 02). This study was continued by characterization of further purified Cps. Mono-derivatization at the reducing end of S-oligoS by uv- absorbing hydrazides was developed. MWt of dansyl-derivatives of Cps was determined by sedimentation equilibrium ultracentrifugation. Overall, results elucidated difference between the structural requirement for anti-CT capacity and that for anti-SF. With the exception of CpX, the high anti-CT potency resided in Cps of -hexadecaS or larger; these also exhibited high anti-SF potency. At MWt <5400, anti-CT capacity decreased sharply, but in this range Cps of 11 to-12mer (-3900) and larger retained high antiSF potency. CpX contained potent 8-to-9mers that comprise <1% of the SP54. These findings confirm our suggestion that the two direct effects of HIV which kill immune cells may be governed by different molecular mechanisms involving S-oligoS, resignaling their potential usefulness in AIDS therapy. 2) Study of inhibition of growth of Kaposi Sarcoma cells in vitro by S-Beta-cyclodextrin (SBCD) was continued, showing inhibitory activity against new cell lines derived from AIDS patients and confirming differences in potency among S-BCD Cps.
