Compositions for promoting HIV-1 virolysis and methods using same

摘要

The present invention includes compounds that are useful for treating or preventing a HIV-1 infection in a mammal. In certain embodiments, the compounds cause cell-free virolysis of an HIV-1 virus. The presented invention further includes a method of causing virolysis of a virus using the compounds described therein. The presented invention further includes a method of treating or preventing an HIV-1 infection in a mammal in need thereof using the compositions described therein.

主权项

1. A compound of formula (I), or a salt or solvate thereof:
BINDER-LINKER-SEQ ID NO:3  (I), wherein in (I) the BINDER binds to gp120, and the LINKER covalently connects the C-terminus of BINDER and the N-terminus of SEQ ID NO:3, wherein the BINDER comprises at least one selected from the group consisting of:
SEQ ID NO:1;SEQ ID NO:12;SEQ ID NO:22 (X1X2X3NIXWX4) (III), wherein in (III)
X1 is absent or E,X2 is selected from the group consisting of F,K,E,R, and Cit,X3 is N or I,X4 is S or T;SEQ ID NO:23 (RINNIXW);SEQ ID NO:24 (INNIXW);SEQ ID NO:25 (NNIXWS);SEQ ID NO:26 (INIXWS);SEQ ID NO:27 (NNIXW);
wherein X is the modified proline of formula (IV)  wherein in (IV) R is selected from the group consisting of naphthyl,p-methyl phenyl, p-ethyl phenyl,2-phenylethyl and metallocene; and wherein the LINKER is a peptide of formula (II):
LINKER1-(LINKER2)n  (II),wherein in (II) the LINKER1 comprises 1 to 60 amino acid residues; the LINKER2 comprises (His)6 (SEQ ID NO:5) or AspTyrLysAspAspAspAspLys (SEQ ID NO:9), and ‘n’ is 0 or 1.