Triple Hyp→Pro replacement in integramide A, a peptaib inhibitor of HIV‐1 integrase: Effect on conformation and bioactivity

Zotti, Marta De; Borggraeve, Wim M. De; Kaptein, Bernard; Broxterman, Quirinus B.; Singh, Sheo B.; Felock, Peter J.; Hazuda, Daria J.; Formaggio, Fernando; Toniolo, Claudio

doi:10.1002/bip.21461

Cited by 3 publications

(1 citation statement)

References 104 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The stereochemical configuration of all the chiral carbons was determined [104], and both integramides were synthesized in solution [105]. Some diastereomeric integramide A analogs containing prolines instead of hydroxyprolines were also synthesized [106]. All of these analogs have similar IN‐inhibitory activity as the parent peptides (IC 50 = 10–30 μ m ).…”

Section: Peptides From Combinatorial Screeningmentioning

confidence: 99%

Peptides that inhibit HIV‐1 integrase by blocking its protein–protein interactions

2012

View full text Add to dashboard Cite

HIV‐1 integrase (IN) is one of the key enzymes in the viral replication cycle. It mediates the integration of viral cDNA into the host cell genome. IN activity requires interactions with several viral and cellular proteins, as well as IN oligomerization. Inhibition of IN is an important target for the development of anti‐HIV therapies, but there is currently only one anti‐HIV drug used in the clinic that targets IN. Several other small‐molecule anti‐IN drug leads are either undergoing clinical trials or in earlier stages of development. These molecules specifically inhibit one of the IN‐mediated reactions necessary for successful integration. However, small‐molecule inhibitors of protein–protein interactions are difficult to develop. In this review, we focus on peptides that inhibit IN. Peptides have advantages over small‐molecule inhibitors of protein–protein interactions: they can mimic the structures of the binding domains within proteins, and are large enough to competitively inhibit protein–protein interactions. The development of peptides that bind IN and inhibit its protein–protein interactions will increase our understanding of the IN mode of action, and lead to the development of new drug leads, such as small molecules derived from these peptides, for better anti‐HIV therapy.

show abstract

Section: Peptides From Combinatorial Screeningmentioning

confidence: 99%

Peptides that inhibit HIV‐1 integrase by blocking its protein–protein interactions

2012

View full text Add to dashboard Cite

show abstract

Design and Discovery of Peptide‐Based HIV‐1 Integrase Inhibitors

Long

Neamati

2011

HIV‐1 Integrase

View full text Add to dashboard Cite

Solution Synthesis, Conformational Analysis, and Antimicrobial Activity of Three Alamethicin F50/5 Analogs Bearing a Trifluoroacetyl Label

Zotti¹,

Ballano²,

Jost³

et al. 2014

Chemistry & Biodiversity

View full text Add to dashboard Cite

We prepared, by solution-phase methods, and fully characterized three analogs of the membrane-active peptaibiotic alamethicin F50/5, bearing a single trifluoroacetyl (Tfa) label at the N-terminus, at position 9 (central region) or at position 19 (C-terminus), and with the three Gln at positions 7, 18, and 19 replaced by Glu(OMe) residues. To add the Tfa label at position 9 or 19, a γ-trifluoroacetylated α,γ-diaminobutyric acid (Dab) residue was incorporated as a replacement for the original Val(9) or Glu(OMe)(19) amino acid. We performed a detailed conformational analysis of the three analogs (using FT-IR absorption, CD, 2D-NMR, and X-ray diffraction), which clearly showed that Tfa labeling does not introduce any dramatic backbone modification in the predominantly α-helical structure of the parent peptaibiotic. The results of an initial solid-state (19)F-NMR study on one of the analogs favor the conclusion that the Tfa group is a very promising reporter for the analysis of peptaibioticmembrane interactions. Finally, we found that the antimicrobial activities of the three newly synthesized analogs depend on the position of the Tfa label in the peptide sequence.

show abstract

Triple Hyp→Pro replacement in integramide A, a peptaib inhibitor of HIV‐1 integrase: Effect on conformation and bioactivity

Cited by 3 publications

References 104 publications

Peptides that inhibit HIV‐1 integrase by blocking its protein–protein interactions

Peptides that inhibit HIV‐1 integrase by blocking its protein–protein interactions

Design and Discovery of Peptide‐Based HIV‐1 Integrase Inhibitors

Solution Synthesis, Conformational Analysis, and Antimicrobial Activity of Three Alamethicin F50/5 Analogs Bearing a Trifluoroacetyl Label

Contact Info

Product

Resources

About