geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Discovery of small-molecule HIV-1 fusion and integrase inhibitors oleuropein and hydroxytyrosol: part II. integrase inhibition


, : Discovery of small-molecule HIV-1 fusion and integrase inhibitors oleuropein and hydroxytyrosol: part II. integrase inhibition. Biochemical and Biophysical Research Communications 354(4): 879-884

We report molecular modeling and functional confirmation of Ole and HT binding to HIV-1 integrase. Docking simulations identified two binding regions for Ole within the integrase active site. Region I encompasses the conserved D64-116-E152 motif, while region II involves the flexible loop region formed by amino acid residues 140-149. HT, on the other hand, binds to region II. Both Ole and HT exhibit favorable interactions with important amino acid residues through strong H-bonding and van der Waals contacts, predicting integrase inhibition. To test and confirm modeling predictions, we examined the effect of Ole and HT on HIV-1 integrase activities including 3'-processing, strand transfer, and disintegration. Ole and HT exhibit dose-dependent inhibition on all three activities, with EC(50)s in the nanomolar range. These studies demonstrate that molecular modeling of target-ligand interaction coupled with structural-activity analysis should facilitate the design and identification of innovative integrase inhibitors and other therapeutics.

US$19.90

PMID: 17261269

DOI: 10.1016/j.bbrc.2007.01.058


Other references

Sagalowsky A.; Wilson T.; Alexander S.; Arant B.; Dawidson I.; Dulzo T.; Levasseur D., 1991: Impact of donor age on pediatric renal transplantation. Journal of Urology 145(4 SUPPL): 303A

Grabowski, T.J.; Damasio, H.; Frank, R.; Boles Ponto, L.L.; Watkins, G.L.; Hichwa, R.D., 1994: Hypothesis-driven neuroanatomical analysis of PET images Validation with retinotopic mapping. Neurology 44(4 SUPPL 2): A262

Kumar, V.; Willshaw, H.E., 2000: Marginal myotomy for residual esotropia - Review of the last decade. IOVS 41(4): S709, March 15

Haritani, M.; Kajigaya, H.; Akashi, T.; Kamemura, M.; Tanahara, N.; Umeda, M.; Sugiyama, M.; Isoda, M.; Kato, C., 1984: A study on the origin of adenocarcinoma in fowls using immunohistological technique. All of 12 hens with adenocarcinoma had lesions in the oviduct, pancreas and mesentery, 6 in the ovaries, 3 in the lungs, 8 in the liver, and 6 in the spleen. By indirect immunofluorescence all tumours tissues were positive for ovalbumin. It is sug...

Tang, J.; Wang, L.; Markiv, A.; Jeffs, S.A.; Dreja, H.; McKnight, Áine.; He, M.; Kang, A.S., 2013: Accessing of recombinant human monoclonal antibodies from patient libraries by eukaryotic ribosome display. What are effective antibodies and when do they arise to prevent or delay disease onset during a natural infection or in the course of vaccination? To address these questions at a molecular level requires longitudinal studies, capturing and analyzi...

Desgrez, P.; Delarue, J., 1972: Jacques Delarue (1901-1971). Annales de Biologie Clinique 30(3): 293-293

Bai, X.F.ng; Liu, J.Q.ng; Bender, J.; Liu, X.; Zheng, H.; Zheng, P.; Liu, Y., 2001: Initiation of CD8 T cell response against tumor antigens in the secondary lymphoid organs in the absence of tumor metastasis. Proceedings of the American Association for Cancer Research Annual Meeting 42: 330, March

Tsimitakis, P., 1961: A contribution to the problem of the pathogenesis and localization of prostatic carcinoma. Zeitschrift für Urologie 54: 471-481

Bargeton, D., 1980: Daniel Bargeton (1906-1980). Bulletin Europeen de Physiopathologie Respiratoire 16(6): 843-845

van Hemmen JL.K.hn, 1986: Nonlinear neural networks. Physical Review Letters 57(7): 913-916