Donzella G A, Schols D, Lin S W, Esté J A, Nagashima K A, Maddon P J, Allaway G P, Sakmar T P, Henson G, De Clercq E, Moore J P
The Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016, USA.
Nat Med. 1998 Jan;4(1):72-7. doi: 10.1038/nm0198-072.
The bicyclam AMD3100 (formula weight 830) blocks HIV-1 entry and membrane fusion via the CXCR4 co-receptor, but not via CCR5. AMD3100 prevents monoclonal antibody 12G5 from binding to CXCR4, but has no effect on binding of monoclonal antibody 2D7 to CCR5. It also inhibits binding of the CXC-chemokine, SDF-1alpha, to CXCR4 and subsequent signal transduction, but does not itself cause signaling and has no effect on RANTES signaling via CCR5. Thus, AMD3100 prevents CXCR4 functioning as both a HIV-1 co-receptor and a CXC-chemokine receptor. Development of small molecule inhibitors of HIV-1 entry is feasible.
双环胺AMD3100（分子式量830）通过CXCR4共受体阻断HIV-1进入和膜融合，但不通过CCR5。AMD3100可阻止单克隆抗体12G5与CXCR4结合，但对单克隆抗体2D7与CCR5的结合没有影响。它还抑制CXC趋化因子SDF-1α与CXCR4的结合及随后的信号转导，但自身不会引发信号，且对通过CCR5的RANTES信号没有影响。因此，AMD3100可阻止CXCR4同时作为HIV-1共受体和CXC趋化因子受体发挥作用。开发HIV-1进入的小分子抑制剂是可行的。
