3l35 | pdb_00003l35

PIE12 D-peptide against HIV entry

spinqualitylabelsall models 3l35, resolution 1.55Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3l35 is a 6 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. NonStd Res: ACE, DAS, DCY, DGL, DGN, DHI, DLE, DLY, DPR, DTR, DTY, NH2 Related: 2r5d, 3l36 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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. Design of a potent D-peptide HIV-1 entry inhibitor with a strong barrier to resistance.,Welch BD, Francis JN, Redman JS, Paul S, Weinstock MT, Reeves JD, Lie YS, Whitby FG, Eckert DM, Hill CP, Root MJ, Kay MS J Virol. 2010 Nov;84(21):11235-44. Epub 2010 Aug 18. PMID:20719956 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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