Dimeric C34 Derivatives Linked through Disulfide Bridges as New HIV-1 Fusion Inhibitors.

Chembiochem 2019 Apr 22. Epub 2019 Apr 22.

Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU), 2-3-10 Kandasurugadai, Chiyoda-ku, Tokyo, 101-0062, Japan.

C34, a 34-mer fragment peptide, is contained in the HIV-1 envelope protein gp41. A dimeric derivative of C34 linked through a disulfide bridge at its C terminus was synthesized and found to display potent anti-HIV activity, comparable with that of a previously reported PEGylated dimer of C34REG. The reduction in the size of the linker moiety for dimerization was thus successful, and this result might shed some light on the mechanism of the suppression of six-helix bundle formation by these C34 dimeric derivatives. Addition of a Gly-Cys(CH CONH )-Gly-Gly motif at the N-terminal position of a C34 monomeric derivative significantly increased the anti-HIV-1 activity. This moiety functions as a new pharmacophore, and this might provide a useful insight into the design of potent HIV-1 fusion inhibitors.

Download full-text PDF

Source
http://dx.doi.org/10.1002/cbic.201900187DOI Listing

Still can't find the full text of the article?

We can help you send a request to the authors directly.
April 2019
2 Reads
3.088 Impact Factor

Publication Analysis

Top Keywords

linked disulfide
8
fusion inhibitors
8
hiv-1 fusion
8
light mechanism
4
successful result
4
dimerization successful
4
result light
4
mechanism suppression
4
c34 dimeric
4
formation c34
4
bundle formation
4
six-helix bundle
4
suppression six-helix
4
moiety dimerization
4
comparable reported
4
activity comparable
4
anti-hiv activity
4
potent anti-hiv
4
reported pegylated
4
pegylated dimer
4

References

(Supplied by CrossRef)

Tamamura H. et al.
2018

Ohashi N. et al.
2017

Similar Publications