HIV-1 Integrase-Targeted Short Peptides Derived from a Viral Protein R Sequence.
Molecules
; 23(8)2018 Jul 26.
Article
in En
| MEDLINE
| ID: mdl-30049955
ABSTRACT
HIV-1 integrase (IN) inhibitors represent a new class of highly effective anti-AIDS therapeutics. Current FDA-approved IN strand transfer inhibitors (INSTIs) share a common mechanism of action that involves chelation of catalytic divalent metal ions. However, the emergence of IN mutants having reduced sensitivity to these inhibitors underlies efforts to derive agents that antagonize IN function by alternate mechanisms. Integrase along with the 96-residue multifunctional accessory protein, viral protein R (Vpr), are both components of the HIV-1 pre-integration complex (PIC). Coordinated interactions within the PIC are important for viral replication. Herein, we report a 7-mer peptide based on the shortened Vpr (69â»75) sequence containing a biotin group and a photo-reactive benzoylphenylalanyl residue, and which exhibits low micromolar IN inhibitory potency. Photo-crosslinking experiments have indicated that the peptide directly binds IN. The peptide does not interfere with IN-DNA interactions or induce higher-order, aberrant IN multimerization, suggesting a mode of action for the peptide that is distinct from clinically used INSTIs and developmental allosteric IN inhibitors. This compact Vpr-derived peptide may serve as a valuable pharmacological tool to identify a potential new pharmacologic site.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peptides
/
HIV Infections
/
HIV-1
/
Gene Products, vpr
/
HIV Integrase Inhibitors
/
HIV Integrase
Language:
En
Journal:
Molecules
Journal subject:
BIOLOGIA
Year:
2018
Type:
Article
Affiliation country:
United States