The aim of the present study was to evaluate the capacity of synthetic l- and d-peptides encompassing the HIV-1BRU gp160 REKR cleavage site to interfere with HIV and simian immuno-deficiency virus (SIV) replication and maturation of the envelope glycoprotein (Env) precursors. To facilitate their penetration into cells, a decanoyl (dec) group was added at the N-terminus. The sequences synthesized included dec5d or dec5l (decREKRV), dec9d or dec9l (decRVVQREKRV) and dec14d or dec14l (TKAKRRVVQREKRV). The peptide dec14d was also prepared with a chloromethane (cmk) group as C-terminus. Because l-peptides exhibit significant cytotoxicity starting at 35μM, further characterization was conducted mostly with d-peptides, which exhibited no cytotoxicity at concentrations higher than 70μM. The data show that only dec14d and dec14dcmk could inhibit HIV-1BRU, HIV-2ROD and SIVmac251 replication and their syncytium-inducing capacities. Whereas peptides dec5d and dec9d were inactive, dec14dcmk was at least twice as active as peptide dec14d. At the molecular level, our data show a direct correlation between anti-viral activity and the ability of the peptides to interfere with maturation of the Env precursors. Furthermore, we show that when tested in vitro the dec14d peptide inhibited PC7 with an inhibition constant Ki = 4.6μM, whereas the peptide dec14l preferentially inhibited furin with a Ki = 28μM. The fact that PC7 and furin are the major prohormone convertases reported to be expressed in T4 lymphocytes, the principal cell targets of HIV, suggests that they are involved in the maturation of HIV and SIV Env precursors.
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September 2002
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Research Article|
September 15 2002
Effects of l- and d-REKR amino acid-containing peptides on HIV and SIV envelope glycoprotein precursor maturation and HIV and SIV replication
Bouchaib BAHBOUHI;
Bouchaib BAHBOUHI
∗Laboratoire d'Immuno-Virologie, EA 30-38 Université Paul Sabatier, UFR/SVT, 118 route de Narbonne 31062 Toulouse, France
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Nathalie CHAZAL;
Nathalie CHAZAL
∗Laboratoire d'Immuno-Virologie, EA 30-38 Université Paul Sabatier, UFR/SVT, 118 route de Narbonne 31062 Toulouse, France
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Nabil Georges SEIDAH;
Nabil Georges SEIDAH
†Laboratory of Biochemical Neuroendocrinology, Montreal, QC, Canada H2W 1R7,
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Cristina CHIVA;
Cristina CHIVA
‡Departament de Quimica Orgànica, Divisio'de Ciències Experimentals i Mathemàtiques, Universitat de Barcelona, Marti’ Franqués, 1—11, E-0828 Barcelona, Spain
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Marcelo KOGAN;
Marcelo KOGAN
‡Departament de Quimica Orgànica, Divisio'de Ciències Experimentals i Mathemàtiques, Universitat de Barcelona, Marti’ Franqués, 1—11, E-0828 Barcelona, Spain
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Fernando ALBERICIO;
Fernando ALBERICIO
‡Departament de Quimica Orgànica, Divisio'de Ciències Experimentals i Mathemàtiques, Universitat de Barcelona, Marti’ Franqués, 1—11, E-0828 Barcelona, Spain
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Ernest GIRALT;
Ernest GIRALT
‡Departament de Quimica Orgànica, Divisio'de Ciències Experimentals i Mathemàtiques, Universitat de Barcelona, Marti’ Franqués, 1—11, E-0828 Barcelona, Spain
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Elmostafa BAHRAOUI
Elmostafa BAHRAOUI
1
∗Laboratoire d'Immuno-Virologie, EA 30-38 Université Paul Sabatier, UFR/SVT, 118 route de Narbonne 31062 Toulouse, France
1To whom correspondence should be addressed (e-mail bahraoui@cict.fr).
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Publisher: Portland Press Ltd
Received:
January 08 2002
Revision Received:
May 23 2002
Accepted:
June 18 2002
Accepted Manuscript online:
June 18 2002
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2002
2002
Biochem J (2002) 366 (3): 863–872.
Article history
Received:
January 08 2002
Revision Received:
May 23 2002
Accepted:
June 18 2002
Accepted Manuscript online:
June 18 2002
Citation
Bouchaib BAHBOUHI, Nathalie CHAZAL, Nabil Georges SEIDAH, Cristina CHIVA, Marcelo KOGAN, Fernando ALBERICIO, Ernest GIRALT, Elmostafa BAHRAOUI; Effects of l- and d-REKR amino acid-containing peptides on HIV and SIV envelope glycoprotein precursor maturation and HIV and SIV replication. Biochem J 15 September 2002; 366 (3): 863–872. doi: https://doi.org/10.1042/bj20020052
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