6TVU

Structure of native gp41 derived peptide fusion inhibitor

This is a non-PDB format compatible entry.

Summary for 6TVU

• Entry DOI: 10.2210/pdb6tvu/pdb
• Descriptor: Env polyprotein (Fragment), Transmembrane protein gp41 (3 entities in total)
• Functional Keywords: inhibitor, helix bundle, hiv, viral protein
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 2
• Total formula weight: 8307.37

Authors

Huhmann, S.,Nyakatura, E.K.,Rohrhofer, A.,Schmidt, B.,Eichler, J.,Moschner, J.,Roth, C.,Koksch, B. (deposition date: 2020-01-10, release date: 2021-01-27, Last modification date: 2023-11-15)

Primary citation

Huhmann, S.,Nyakatura, E.K.,Rohrhofer, A.,Moschner, J.,Schmidt, B.,Eichler, J.,Roth, C.,Koksch, B.
Systematic Evaluation of Fluorination as Modification for Peptide-Based Fusion Inhibitors against HIV-1 Infection.
Chembiochem, 22:3443-3451, 2021

PubMed Abstract: With the emergence of novel viruses, the development of new antivirals is more urgent than ever. A key step in human immunodeficiency virus type 1 (HIV-1) infection is six-helix bundle formation within the envelope protein subunit gp41. Selective disruption of bundle formation by peptides has been shown to be effective; however, these drugs, exemplified by T20, are prone to rapid clearance from the patient. The incorporation of non-natural amino acids is known to improve these pharmacokinetic properties. Here, we evaluate a peptide inhibitor in which a critical Ile residue is replaced by fluorinated analogues. We characterized the influence of the fluorinated analogues on the biophysical properties of the peptide. Furthermore, we show that the fluorinated peptides can block HIV-1 infection of target cells at nanomolar levels. These findings demonstrate that fluorinated amino acids are appropriate tools for the development of novel peptide therapeutics.

PubMed: 34605595
DOI: 10.1002/cbic.202100417

Experimental method

X-RAY DIFFRACTION (1.25 Å)