title: Fullerene-based inhibitors of HIV-1 protease.
abstract: A series of Fmoc-Phe(4-aza-C60)-OH of fullerene amino acid derived peptides have been prepared by solid phase peptide synthesis, in which the terminal amino acid, Phe(4-aza-C60)-OH, is derived from the dipolar addition to C60 of the Fmoc-Nα-protected azido amino acids derived from phenylalanine: Fmoc-Phe(4-aza-C60)-Lys3-OH (1), Fmoc-Phe(4-aza-C60)-Pro-Hyp-Lys-OH (2), and Fmoc-Phe(4-aza-C60)-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 C60-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.
authors.affiliation: Department of Chemistry, Rice University, Houston, TX, 77005, USA.
authors.forename: T Amanda
authors.initials: TA
authors.lastname: Strom
authors.affiliation: Department of Biophysics, School of Medicine, Bahcesehir University, Istanbul, Turkey.|Department of Biological Sciences, Institute for Biocomplexity and Informatics, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Serdar
authors.initials: S
authors.lastname: Durdagi
authors.affiliation: School of Medicine, Bahcesehir University, Istanbul, Turkey.
authors.forename: Suha Salih
authors.initials: SS
authors.lastname: Ersoz
authors.affiliation: Department of Biophysics, School of Medicine, Bahcesehir University, Istanbul, Turkey.
authors.forename: Ramin Ekhteiari
authors.initials: RE
authors.lastname: Salmas
authors.affiliation: Laboratorio di Chimica Bioinorganica, Università degli Studi di Firenze, Rm. 188, Via della Lastruccia 3, I-50019, Sesto Fiorentino (Firenze), Italy.
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
authors.affiliation: Department of Chemistry, Rice University, Houston, TX, 77005, USA.|Department of Materials Science and Nanoengineering, Rice University, Houston, TX, 77005, USA.|Institute of Life Sciences, Swansea University, Singleton Park, Swansea, SA2 8PP, Wales, UK.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Barron
mesh_terms: D000595:Amino Acid Sequence; D020134:Catalytic Domain / Q000187:drug effects; D037741:Fullerenes / Q000737:chemistry*; D016333:HIV Protease / Q000737:chemistry* / Q000378:metabolism; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D037741:Fullerenes; D011480:Protease Inhibitors; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1
keywords: C60; HIV-1; computation; fullerene; inhibitor; solid phase peptide synthesis