Unknown

Dataset Information

0

A large library based on a novel (CH2) scaffold: identification of HIV-1 inhibitors.

ABSTRACT: Isolated immunoglobulin CH2 domains were proposed as scaffolds for selection of binders with potential effector functions. We tested the feasibility of this approach by constructing a large (size 5 x 10(10)) library where all amino acids in two loops (BC and FG) were mutated to four residues (Y, A, D, or S). Three binders were selected from this library by panning against a gp120-CD4 complex. The strongest binder, m1a1, recognized specifically a highly conserved CD4i epitope and inhibited to various extents seven out of nine HIV-1 isolates from different clades. The loop BC and the conformational state of the scaffold are critical for its binding. These results provide a proof of concept for the potential of CH2 as a scaffold for construction of libraries containing potentially useful binders. The newly identified HIV-1 inhibitors could be further improved to candidate therapeutics and/or used as research reagents for exploration of conserved gp120 structures.

SUBMITTER: Xiao X 

PROVIDER: S-EPMC2753272 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

A large library based on a novel (CH2) scaffold: identification of HIV-1 inhibitors.

Xiao Xiaodong X   Feng Yang Y   Vu Bang K BK   Ishima Rieko R   Dimitrov Dimiter S DS  

Biochemical and biophysical research communications 20090715 2

Isolated immunoglobulin CH2 domains were proposed as scaffolds for selection of binders with potential effector functions. We tested the feasibility of this approach by constructing a large (size 5 x 10(10)) library where all amino acids in two loops (BC and FG) were mutated to four residues (Y, A, D, or S). Three binders were selected from this library by panning against a gp120-CD4 complex. The strongest binder, m1a1, recognized specifically a highly conserved CD4i epitope and inhibited to var  ...[more]

Similar Datasets

Unknown Identification of Protein Palmitoylation Inhibitors from a Scaffold Ranking Library.
| S-EPMC5068503 | biostudies-literature
Unknown Scaffold Repurposing of in-House Chemical Library toward the Identification of New Casein Kinase 1 δ Inhibitors.
| S-EPMC7294733 | biostudies-literature
Unknown Discovery of novel SERCA inhibitors by virtual screening of a large compound library.
| S-EPMC3065555 | biostudies-literature
Unknown Identification of Novel 3-Hydroxy-pyran-4-One Derivatives as Potent HIV-1 Integrase Inhibitors Using <i>in silico</i> Structure-Based Combinatorial Library Design Approach.
| S-EPMC6700280 | biostudies-literature
Unknown An Isoquinoline Scaffold as a Novel Class of Allosteric HIV-1 Integrase Inhibitors.
| S-EPMC6378678 | biostudies-literature
Unknown Structure-Based Scaffold Repurposing toward the Discovery of Novel Cholinesterase Inhibitors.
| S-EPMC7726787 | biostudies-literature
Unknown Large library docking for novel SARS-CoV-2 main protease non-covalent and covalent inhibitors.
| S-EPMC10364469 | biostudies-literature
Unknown Virtual screening based identification of novel small-molecule inhibitors targeted to the HIV-1 capsid.
| S-EPMC3034313 | biostudies-literature
Unknown Synthesis of New DPP-4 Inhibitors Based on a Novel Tricyclic Scaffold.
| S-EPMC4360159 | biostudies-literature
Unknown Identification and Characterizations of Novel, Selective Histone Methyltransferase SET7 Inhibitors by Scaffold Hopping- and 2D-Molecular Fingerprint-Based Similarity Search.
| S-EPMC6017732 | biostudies-literature