3L35: Pie12 D-Peptide Against Hiv Entry

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.
PDB ID: 3L35Download
MMDB ID: 85900
PDB Deposition Date: 2009/12/16
Updated in MMDB: 2010/11
Experimental Method:
x-ray diffraction
Resolution: 1.55  Å
Similar Structures:
Biological Unit for 3L35: hexameric; determined by author and by software (PISA)
Molecular Components in 3L35
Label Count Molecule
Proteins (3 molecules)
Gp41 N-peptide
Molecule annotation
Nucleotide(1 molecule)
HIV Entry Inhibitor Pie12
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB