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Fullerene‐based inhibitors of HIV‐1 protease
Author(s) -
Strom T. Amanda,
Durdagi Serdar,
Ersoz Suha Salih,
Salmas Ramin Ekhteiari,
Supuran Claudiu T.,
Barron Andrew R.
Publication year - 2015
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.2828
Subject(s) - chemistry , peptide , amino acid , protease , stereochemistry , phenylalanine , docking (animal) , combinatorial chemistry , enzyme , biochemistry , medicine , nursing
A series of Fmoc‐Phe(4‐aza‐C 60 )‐OH of fullerene amino acid derived peptides have been prepared by solid phase peptide synthesis, in which the terminal amino acid, Phe(4‐aza‐C 60 )‐OH, is derived from the dipolar addition to C 60 of the Fmoc‐Nα‐protected azido amino acids derived from phenylalanine: Fmoc‐Phe(4‐aza‐C 60 )‐Lys 3 ‐OH ( 1 ), Fmoc‐Phe(4‐aza‐C 60 )‐Pro‐Hyp‐Lys‐OH ( 2 ), and Fmoc‐Phe(4‐aza‐C 60 )‐Hyp‐Hyp‐Lys‐OH ( 3 ). The inhibition constant of our fullerene aspartic protease PRIs utilized FRET‐based assay to evaluate the enzyme kinetics of HIV‐1 PR at various concentrations of inhibitors. Simulation of the docking of the peptide Fmoc‐Phe‐Pro‐Hyp‐Lys‐OH overestimated the inhibition, while the amino acid PRIs were well estimated. The experimental results show that C 60 ‐based amino acids are a good base structure in the design of protease inhibitors and that their inhibition can be improved upon by the addition of designer peptide sequences. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.