Elucidation of New Binding Interactions with the Tumor Susceptibility Gene 101 (Tsg101) Protein Using Modified HIV-1 Gag-p6 Derived Peptide Ligands.

摘要: Targeting protein-protein interactions is gaining greater recognition as an attractive approach to therapeutic development. An example of this may be found with the human cellular protein encoded by tumor susceptibility gene 101 (Tsg101), where interaction p6 C-terminal domain nascent viral Gag required for HIV-1 particle budding and release. This association Tsg101 highly dependent on a "Pro-Thr-Ala-Pro" ("PTAP") peptide sequence within protein. Although p6-derived peptides offer potential starting points developing Tsg101-binding inhibitors, affinities canonical are outside useful range (K(d) values than 50 μM). Reported herein crystal structures in complex two structurally-modified PTAP-derived peptides. data define new regions ligand not previously identified sequences. information could design antagonists.