Anionic Carbosilane Dendrimers Destabilize the GP120-CD4 Complex Blocking HIV-1 Entry and Cell to Cell Fusion

Carlos Guerrero-Beltran, Ignacio Rodriguez-Izquierdo, Ma Jesus Serramia, Ingrid Araya-Durán, Valeria Márquez-Miranda, Rafael Gomez, Francisco Javier De La Mata, Manuel Leal, Fernando González-Nilo, M. Angeles Muñoz-Fernández

Resultado de la investigación: Article

Resumen

Cell-to-cell transmission is the most effective pathway for the spread of human immunodeficiency virus (HIV-1). Infected cells expose virus-encoded fusion proteins on their surface as a consequence of HIV-1 replicative cycle that interacts with noninfected cells through CD4 receptor and CXCR4 coreceptor leading to the formation of giant multinucleated cells known as syncytia. Our group previously described the potent activity of dendrimers against CCR5-tropic viruses. Nevertheless, the study of G1-S4, G2-S16, and G3-S16 dendrimers in the context of X4-HIV-1 tropic cell-cell fusion referred to syncytium formation remains still unknown. These dendrimers showed a suitable biocompatibility in all cell lines studied and our results demonstrated that anionic carbosilane dendrimers G1-S4, G2-S16, and G3-S16 significantly inhibit the X4-HIV-1 infection, as well as syncytia formation, in a dose dependent manner. We also demonstrated that G2-S16 and G1-S4 significantly reduced syncytia formation in HIV-1 Env-mediated cell-to-cell fusion model. Molecular modeling and in silico models showed that G2-S16 dendrimer interfered with gp120-CD4 complex and demonstrated its potential use for a treatment.

IdiomaEnglish
Páginas1584-1594
Número de páginas11
PublicaciónBioconjugate Chemistry
Volumen29
Número de edición5
DOI
EstadoPublished - 16 may 2018

Huella dactilar

Dendrimers
Cell Fusion
Giant Cells
HIV-1
Fusion reactions
Viruses
Tropics
Cells
CD4 Antigens
Viral Fusion Proteins
Molecular modeling
Biocompatibility
Computer Simulation
HIV Infections
carbosilane
Proteins
Cell Line

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

Citar esto

Guerrero-Beltran, C., Rodriguez-Izquierdo, I., Serramia, M. J., Araya-Durán, I., Márquez-Miranda, V., Gomez, R., ... Muñoz-Fernández, M. A. (2018). Anionic Carbosilane Dendrimers Destabilize the GP120-CD4 Complex Blocking HIV-1 Entry and Cell to Cell Fusion. Bioconjugate Chemistry, 29(5), 1584-1594. https://doi.org/10.1021/acs.bioconjchem.8b00106
Guerrero-Beltran, Carlos ; Rodriguez-Izquierdo, Ignacio ; Serramia, Ma Jesus ; Araya-Durán, Ingrid ; Márquez-Miranda, Valeria ; Gomez, Rafael ; De La Mata, Francisco Javier ; Leal, Manuel ; González-Nilo, Fernando ; Muñoz-Fernández, M. Angeles. / Anionic Carbosilane Dendrimers Destabilize the GP120-CD4 Complex Blocking HIV-1 Entry and Cell to Cell Fusion. En: Bioconjugate Chemistry. 2018 ; Vol. 29, N.º 5. pp. 1584-1594.
@article{90de08982fe9434284341ccc2396c7b6,
title = "Anionic Carbosilane Dendrimers Destabilize the GP120-CD4 Complex Blocking HIV-1 Entry and Cell to Cell Fusion",
abstract = "Cell-to-cell transmission is the most effective pathway for the spread of human immunodeficiency virus (HIV-1). Infected cells expose virus-encoded fusion proteins on their surface as a consequence of HIV-1 replicative cycle that interacts with noninfected cells through CD4 receptor and CXCR4 coreceptor leading to the formation of giant multinucleated cells known as syncytia. Our group previously described the potent activity of dendrimers against CCR5-tropic viruses. Nevertheless, the study of G1-S4, G2-S16, and G3-S16 dendrimers in the context of X4-HIV-1 tropic cell-cell fusion referred to syncytium formation remains still unknown. These dendrimers showed a suitable biocompatibility in all cell lines studied and our results demonstrated that anionic carbosilane dendrimers G1-S4, G2-S16, and G3-S16 significantly inhibit the X4-HIV-1 infection, as well as syncytia formation, in a dose dependent manner. We also demonstrated that G2-S16 and G1-S4 significantly reduced syncytia formation in HIV-1 Env-mediated cell-to-cell fusion model. Molecular modeling and in silico models showed that G2-S16 dendrimer interfered with gp120-CD4 complex and demonstrated its potential use for a treatment.",
author = "Carlos Guerrero-Beltran and Ignacio Rodriguez-Izquierdo and Serramia, {Ma Jesus} and Ingrid Araya-Dur{\'a}n and Valeria M{\'a}rquez-Miranda and Rafael Gomez and {De La Mata}, {Francisco Javier} and Manuel Leal and Fernando Gonz{\'a}lez-Nilo and Mu{\~n}oz-Fern{\'a}ndez, {M. Angeles}",
year = "2018",
month = "5",
day = "16",
doi = "10.1021/acs.bioconjchem.8b00106",
language = "English",
volume = "29",
pages = "1584--1594",
journal = "Bioconjugate Chemistry",
issn = "1043-1802",
publisher = "American Chemical Society",
number = "5",

}

Guerrero-Beltran, C, Rodriguez-Izquierdo, I, Serramia, MJ, Araya-Durán, I, Márquez-Miranda, V, Gomez, R, De La Mata, FJ, Leal, M, González-Nilo, F & Muñoz-Fernández, MA 2018, 'Anionic Carbosilane Dendrimers Destabilize the GP120-CD4 Complex Blocking HIV-1 Entry and Cell to Cell Fusion' Bioconjugate Chemistry, vol. 29, n.º 5, pp. 1584-1594. https://doi.org/10.1021/acs.bioconjchem.8b00106

Anionic Carbosilane Dendrimers Destabilize the GP120-CD4 Complex Blocking HIV-1 Entry and Cell to Cell Fusion. / Guerrero-Beltran, Carlos; Rodriguez-Izquierdo, Ignacio; Serramia, Ma Jesus; Araya-Durán, Ingrid; Márquez-Miranda, Valeria; Gomez, Rafael; De La Mata, Francisco Javier; Leal, Manuel; González-Nilo, Fernando; Muñoz-Fernández, M. Angeles.

En: Bioconjugate Chemistry, Vol. 29, N.º 5, 16.05.2018, p. 1584-1594.

Resultado de la investigación: Article

TY - JOUR

T1 - Anionic Carbosilane Dendrimers Destabilize the GP120-CD4 Complex Blocking HIV-1 Entry and Cell to Cell Fusion

AU - Guerrero-Beltran, Carlos

AU - Rodriguez-Izquierdo, Ignacio

AU - Serramia, Ma Jesus

AU - Araya-Durán, Ingrid

AU - Márquez-Miranda, Valeria

AU - Gomez, Rafael

AU - De La Mata, Francisco Javier

AU - Leal, Manuel

AU - González-Nilo, Fernando

AU - Muñoz-Fernández, M. Angeles

PY - 2018/5/16

Y1 - 2018/5/16

N2 - Cell-to-cell transmission is the most effective pathway for the spread of human immunodeficiency virus (HIV-1). Infected cells expose virus-encoded fusion proteins on their surface as a consequence of HIV-1 replicative cycle that interacts with noninfected cells through CD4 receptor and CXCR4 coreceptor leading to the formation of giant multinucleated cells known as syncytia. Our group previously described the potent activity of dendrimers against CCR5-tropic viruses. Nevertheless, the study of G1-S4, G2-S16, and G3-S16 dendrimers in the context of X4-HIV-1 tropic cell-cell fusion referred to syncytium formation remains still unknown. These dendrimers showed a suitable biocompatibility in all cell lines studied and our results demonstrated that anionic carbosilane dendrimers G1-S4, G2-S16, and G3-S16 significantly inhibit the X4-HIV-1 infection, as well as syncytia formation, in a dose dependent manner. We also demonstrated that G2-S16 and G1-S4 significantly reduced syncytia formation in HIV-1 Env-mediated cell-to-cell fusion model. Molecular modeling and in silico models showed that G2-S16 dendrimer interfered with gp120-CD4 complex and demonstrated its potential use for a treatment.

AB - Cell-to-cell transmission is the most effective pathway for the spread of human immunodeficiency virus (HIV-1). Infected cells expose virus-encoded fusion proteins on their surface as a consequence of HIV-1 replicative cycle that interacts with noninfected cells through CD4 receptor and CXCR4 coreceptor leading to the formation of giant multinucleated cells known as syncytia. Our group previously described the potent activity of dendrimers against CCR5-tropic viruses. Nevertheless, the study of G1-S4, G2-S16, and G3-S16 dendrimers in the context of X4-HIV-1 tropic cell-cell fusion referred to syncytium formation remains still unknown. These dendrimers showed a suitable biocompatibility in all cell lines studied and our results demonstrated that anionic carbosilane dendrimers G1-S4, G2-S16, and G3-S16 significantly inhibit the X4-HIV-1 infection, as well as syncytia formation, in a dose dependent manner. We also demonstrated that G2-S16 and G1-S4 significantly reduced syncytia formation in HIV-1 Env-mediated cell-to-cell fusion model. Molecular modeling and in silico models showed that G2-S16 dendrimer interfered with gp120-CD4 complex and demonstrated its potential use for a treatment.

UR - http://www.scopus.com/inward/record.url?scp=85047260448&partnerID=8YFLogxK

U2 - 10.1021/acs.bioconjchem.8b00106

DO - 10.1021/acs.bioconjchem.8b00106

M3 - Article

VL - 29

SP - 1584

EP - 1594

JO - Bioconjugate Chemistry

T2 - Bioconjugate Chemistry

JF - Bioconjugate Chemistry

SN - 1043-1802

IS - 5

ER -

Guerrero-Beltran C, Rodriguez-Izquierdo I, Serramia MJ, Araya-Durán I, Márquez-Miranda V, Gomez R y otros. Anionic Carbosilane Dendrimers Destabilize the GP120-CD4 Complex Blocking HIV-1 Entry and Cell to Cell Fusion. Bioconjugate Chemistry. 2018 may 16;29(5):1584-1594. https://doi.org/10.1021/acs.bioconjchem.8b00106