Short peptides with induced beta-turn inhibit the interaction between HIV-1 gp120 and CD4

To identify novel peptides that inhibit the interaction between human immun odeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 and CD4, we co nstructed a targeted phage-displayed peptide library in which phenylalanine and proline were fixed at the fourth and sixth positions, respectively, be cause Phe43 and the adjacent beta -turn of CD4 are critical for interaction with gp120. Two synthetic peptides were selected after three rounds of bio panning against gp120, and one of them, G1 peptide (ARQPSFDLQCGF), exhibite d specific inhibition of the interaction between gp120 and CD4 with an IC50 Of about 50 muM. Structural analysis using NMR demonstrated that G1 peptid e forms a compact cyclic structure similar to the CD4 region interacting wi th gp120. Two derivatives of G1 peptide, a linear hexameric peptide (G1-6) and a cyclic nonameric peptide (G1-c), were synthesized based on the struct ure of the G1 peptide. Interestingly, they showed higher inhibitory activit ies than did G1 peptide with IC50's Of 6 and 1 muM, respectively. Thus, thi s study might provide a new insight into the development of anti-HIV-l inhi bitors.