In this chapter, we describe an algorithm for the design of lead-generation libraries required in combinatorial drug discovery. This algorithm addresses simultaneously the two key criteria of diversity and representativeness of compounds in the resulting library and is computa ...
Advancements in combinatorial chemistry and high-throughput screening technology have enabled the synthesis and screening of large molecular libraries for the purposes of drug discovery. Contrary to initial expectations, the increase in screening library size, typically c ...
This chapter provides a brief overview of chemoinformatics and its applications to chemical library design. It is meant to be a quick starter and to serve as an invitation to readers for more in-depth exploration of the field. The topics covered in this chapter are chemical representation, chemi ...
High-throughput chemistry (HTC) is approaching its 20-year anniversary. Since 1992, some 5,000 chemical libraries, prepared for the purpose of biological intestigation and drug discovery, have been published in the scientific literature. This review highlights the key events in t ...
We present here a workflow for designing a kinase-targeted library (KTL) with the goal of capturing known kinase inhibitor chemical space. We validated our design retrospectively using recent, high-throughput screening data and found significant enrichment of kinase inhibitor h ...
PGVL Hub is an integrated molecular design desktop tool that has been developed and globally deployed throughout Pfizer discovery research units to streamline the design and synthesis of combinatorial libraries and singleton compounds. This tool supports various workflows for d ...
PGVL Hub is a Pfizer internal desktop tool for chemical library and singleton design. In this chapter, we give a short introduction to PGVL Hub, the core workflow it supports, and the rich design capabilities it provides. By re-creating two legacy targeted libraries against the human checkpoint k ...
Combinatorial chemistry with two or more diversity points often leads to an immense number of theoretical products. It is sensible to select the reagents based on the desired properties of the products in the hope of maximizing the usefulness of the synthesized molecules. The presented tool e ...
CLEVER is a computational tool designed to support the creation, manipulation, enumeration, and visualization of combinatorial libraries. The system also provides a summary of the diversity, coverage, and distribution of selected compound collections. When deployed in conjun ...
There are several in vitro cell models for studying the interactions of carbon nanotubes (CNTs) with biological systems. This chapter provides a detailed protocol for studying the effects of CNTs on cell adhesion and spreading. The protocol is a combination of methods of electron microsco ...
High-density carbon nanotube (CNT)-coated surfaces are highly neuro-adhesive. When shaped into regular arrays of isolated islands on a non-adhesive support substrate (such as a clean glass), CNTs can function as effective encoring sites for neurons and glia cells for in-vitro applica ...
The advantages of carbon nanotubes, such as high surface area, favorable electronic properties, and electrocatalytic effect, attracted considerable attention very recently for the construction of electrochemical biosensors. We describe here the construction and applic ...
We describe in this chapter the preparation of simple and cheap carbon nanotube-based biosensor for sensing of glucose. Such biosensor is based on coupling carbon nanotubes and glucose oxidase.
We describe in detail the different steps involved in the construction of a carbon nanotube field-effect transistor (CNTFET) based on a network of single-walled carbon nanotubes (SWCNTs), which can selectively detect human immunoglobulin G (HIgG). HIgG antibodies, which are strongly ...
Surface plasmon resonance is a valuable tool to determine the affinity between glycoconjugates and sugar-binding proteins such as plant and animal lectins. The main interest of using such an approach is that neither the lectins – which are proteins – nor their ligands – natural compounds such as ...
In this chapter, we discuss in detail the fabrication of carbon nanotube biosensors that use a single-walled carbon nanotube field-effect transistor (SWNT-FET) as a transducer, and aptamers as molecular recognition elements. We use a patterned growth technique to grow SWNTs on Si/SiO2 su ...
Surface plasmon resonance has become one of the most important techniques for studying bimolecular interactions. Most of the researchers are using it to study protein–protein interactions, but in recent years membrane model systems have also become available and this makes it possib ...
When designing DNA biosensors, the immobilization of specific DNA probes is one of the most essential parts. Unfortunately, many of the existing strategies (e.g., adsorption, complexation, and entrapment) can only be used on standard microscope slides, while for more tailored surfaces a ...
Qualitative and quantitative aspects of protein interactions with membranes may be studied by optical sensors. Biacore offers two dedicated chips for working with lipids and membranes: the L1 and HPA sensor chips. The L1 chip is the most frequently used in protein–membrane interaction st ...
Surface plasmon resonance (SPR) spectroscopy is emerging as a useful tool for determination of molecular interactions in real time. Studies on the molecular pathogenesis of amyloidoses have shown that the plasma membrane plays an important role in amyloidogenesis and cytotoxicity ...