scholarly journals Novel In Vitro Screening System Based on Differential Scanning Fluorimetry to Search for Small Molecules against the Disassembly or Assembly of HIV-1 Capsid Protein

2017 ◽  
Vol 8 ◽  
Author(s):  
Yasuyuki Miyazaki ◽  
Naoya Doi ◽  
Takaaki Koma ◽  
Akio Adachi ◽  
Masako Nomaguchi
Keyword(s):  
Small Molecules ◽  
Capsid Protein ◽  
In Vitro Screening ◽  
Screening System ◽  
Differential Scanning Fluorimetry ◽  
Hiv 1

An in vitro screening system for characterizing the cleft palate-inducing potential of chemicals and underlying mechanisms

2001 ◽  
Vol 15 (6) ◽  
pp. 665-672 ◽  
Author(s):  
Naoko Shimizu ◽  
Hiroaki Aoyama ◽  
Noriyuki Hatakenaka ◽  
Masahiro Kaneda ◽  
Shoji Teramoto
Keyword(s):  
Cleft Palate ◽  
In Vitro Screening ◽  
Screening System ◽  
Underlying Mechanisms

Synthesis and in Vitro Screening of New Series of 2,6-Dipeptidyl-anthraquinones: Influence of Side Chain Length on HIV-1 Nucleocapsid Inhibitors

2016 ◽  
Vol 59 (5) ◽  
pp. 1914-1924 ◽  
Author(s):  
Francesco Frecentese ◽  
Alice Sosic ◽  
Irene Saccone ◽  
Elia Gamba ◽  
Kristina Link ◽  
...  
Keyword(s):  
Chain Length ◽  
Side Chain ◽  
In Vitro Screening ◽  
Side Chain Length ◽  
Hiv 1

An alternative strategy for inhibiting multidrug-resistant mutants of the dimeric HIV-1 protease by targeting the subunit interface

2007 ◽  
Vol 35 (3) ◽  
pp. 551-554 ◽  
Author(s):  
L. Bannwarth ◽  
M. Reboud-Ravaux
Keyword(s):  
Small Molecules ◽  
Protein Interactions ◽  
Active Site ◽  
Multidrug Resistant ◽  
Cross Resistance ◽  
Mechanism Of Inhibition ◽  
Therapeutic Molecules ◽  
Β Sheet ◽  
Hiv 1

Mutations that occur in response to the HIV-1 protease inhibitors are responsible for the development of multidrug cross-resistance to these antiproteases in AIDS treatment. One alternative to inhibiting the active site of HIV-1 protease is to target the dimer interface of the homodimeric enzyme at the antiparallel β-sheet formed by the interdigitation of the C- and N-ends of each monomer. This region is highly conserved and is responsible for approx. 75% of the dimer-stabilization energy. The strategies that have been used to design small molecules to target the interface antiparallel β-sheet have produced lipopeptides, guanidinium derivatives and peptides (or peptidomimetics) cross-linked with spacers. The mechanism of inhibition was determined using a combination of kinetic and biophysical methods. These dimerization inhibitors proved equally active in vitro against both wild-type and mutated proteases. They are therefore promising alternatives to active-site-directed inhibitors in AIDS therapy. Disruption of protein–protein interactions by small molecules is a new way to obtain potentially therapeutic molecules.

scholarly journals HIV-1 Capsid Protein Forms Spherical (Immature-Like) and Tubular (Mature-Like) Particles in Vitro: Structure Switching by pH-induced Conformational Changes

2001 ◽  
Vol 81 (1) ◽  
pp. 586-594 ◽  
Author(s):  
Lorna S. Ehrlich ◽  
Tianbo Liu ◽  
Suzanne Scarlata ◽  
Benjamin Chu ◽  
Carol A. Carter
Keyword(s):  
Capsid Protein ◽  
Conformational Changes ◽  
Structure Switching ◽  
Hiv 1

Cytostatic Activity of Inorganic Heterocycles in an in vitro Screening System

Oncology ◽  
1983 ◽  
Vol 40 (4) ◽  
pp. 301-304 ◽  
Author(s):  
H.B. Lamberts ◽  
A. van der Meer-Kalverkamp ◽  
J.C. van de Grampel ◽  
A.A. van der Huizen ◽  
A.P. Jekel ◽  
...  
Keyword(s):  
Cytostatic Activity ◽  
In Vitro Screening ◽  
Screening System

Structural determinants of virion assembly and release in the C-terminus of the M-PMV capsid protein

2021 ◽  
Author(s):  
Marlene V. Buckmaster ◽  
Kaneil K. Zadrozny ◽  
Barbie K. Ganser-Pornillos ◽  
Owen Pornillos ◽  
Stephen P. Goff
Keyword(s):  
Capsid Protein ◽  
Conformational Changes ◽  
Structural Determinants ◽  
Particle Assembly ◽  
Gag Protein ◽  
Virion Assembly ◽  
C Terminus ◽  
Hiv 1

The transition from an immature to a fully infectious mature retrovirus particle is associated with molecular switches that trigger dramatic conformational changes in the structure of the Gag proteins. A dominant maturation switch that stabilizes the immature capsid lattice is located downstream of the capsid (CA) protein in many retroviral Gags. The HIV-1 Gag contains a stretch of five amino acid residues termed the ‘clasp motif’, important for the organization of the hexameric subunits that provide stability to the overall immature HIV-1 shell. Sequence alignment of the CA C-terminal domains (CTDs) of the HIV-1 and Mason-Pfizer Monkey Virus (M-PMV) highlighted a spacer-like domain in M-PMV that may provide comparable function. The importance of the sequences spanning the CA-NC cleavage has been demonstrated by mutagenesis, but the specific requirements for the clasp motif in several steps of M-PMV particle assembly and maturation have not been determined in detail. In the present study we report an examination of the role of the clasp motif in the M-PMV life cycle. We generated a series of M-PMV Gag mutants and assayed for assembly of the recombinant protein in vitro , and for the assembly, maturation, release, genomic RNA packaging, and infectivity of the mutant virus in vivo . The mutants revealed major defects in virion assembly and release in 293T and HeLa cells, and even larger defects in infectivity. Our data identifies the clasp motif as a fundamental contributor to CA-CTD interactions necessary for efficient viral infection. Importance The C-terminal domain of the capsid protein of many retroviruses has been shown to be critical for virion assembly and maturation, but the functions of this region of M-PMV are uncertain. We show that a short ‘clasp’ motif in the capsid domain of the M-PMV Gag protein plays a key role in M-PMV virion assembly, genome packaging, and infectivity.

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