3L36

PIE12 D-peptide against HIV entry

Summary for 3L36

• Entry DOI: 10.2210/pdb3l36/pdb
• Related: 2R5D 3L34 3L36
• Descriptor: GP41 N-PEPTIDE, HIV ENTRY INHIBITOR PIE12, 3-CYCLOHEXYL-1-PROPYLSULFONIC ACID, ... (4 entities in total)
• Functional Keywords: coiled-coil, d-peptide inhibitor, de novo protein
• Total number of polymer chains: 2
• Total formula weight: 7660.14

Authors

Welch, B.D.,Redman, J.S.,Paul, S.,Whitby, F.G.,Weinstock, M.T.,Reeves, J.D.,Lie, Y.S.,Eckert, D.M.,Hill, C.P.,Root, M.J.,Kay, M.S. (deposition date: 2009-12-16, release date: 2010-11-03, Last modification date: 2024-11-27)

Primary citation

Welch, B.D.,Francis, J.N.,Redman, J.S.,Paul, S.,Weinstock, M.T.,Reeves, J.D.,Lie, Y.S.,Whitby, F.G.,Eckert, D.M.,Hill, C.P.,Root, M.J.,Kay, M.S.
Design of a potent D-peptide HIV-1 entry inhibitor with a strong barrier to resistance.
J.Virol., 84:11235-11244, 2010

PubMed Abstract: The HIV gp41 N-trimer pocket region is an ideal viral target because it is extracellular, highly conserved, and essential for viral entry. Here, we report on the design of a pocket-specific D-peptide, PIE12-trimer, that is extraordinarily elusive to resistance and characterize its inhibitory and structural properties. D-peptides (peptides composed of D-amino acids) are promising therapeutic agents due to their insensitivity to protease degradation. PIE12-trimer was designed using structure-guided mirror-image phage display and linker optimization and is the first D-peptide HIV entry inhibitor with the breadth and potency required for clinical use. PIE12-trimer has an ultrahigh affinity for the gp41 pocket, providing it with a reserve of binding energy (resistance capacitor) that yields a dramatically improved resistance profile compared to those of other fusion inhibitors. These results demonstrate that the gp41 pocket is an ideal drug target and establish PIE12-trimer as a leading anti-HIV antiviral candidate.

PubMed: 20719956
DOI: 10.1128/JVI.01339-10

Experimental method

X-RAY DIFFRACTION (1.45 Å)