Synthesis of an Artificial gp41-C34 Trimer as an HIV-1 Fusion Inhibitor

The trimer form of the human immunodeficiency virus type a (HIV-1) envelope protein gp41 plays pivotal role in HIV-1 entry. The gp41 is composed with trimers of the N-terminal and C-terminal helical region (NHR and CHR), which form a six-helical bundle (6HB) in the membrane fusion step. A trimeric peptide was synthesized using a C34 derived from CHR using a newly designed template with three equivalent linkers. The C34 trimer induced neutralizing antibodies which can recognize the structure of the C34 trimer. Besides, the C34 trimer showed 100-fold unexpectedly higher anti-HIV-1 activity than the C34 monomer, indicating that a trimeric form is critical for its inhibitory activity.