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Genome Size and the Evolution of New Genes

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Efficient Sampling of Genetically Encoded Biosensor Design Space Enabled with a Design of Experiments and Automation Workflow

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Expanding the Chemical Diversity of Genetically Encoded Libraries.

Sabrina E Iskandar¹, Victoria A Haberman¹, Albert A Bowers^1,2,3

¹Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, United States.

ACS Combinatorial Science

|November 10, 2020

Summary

Researchers are expanding the genetic code to create novel molecular libraries for drug discovery. This review covers chemical methods, their limitations, and assessment strategies for enhanced therapeutic target development.

Keywords:

chemical modification display technologies genetically encoded libraries peptide libraries quality control metrics unnatural amino acids

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Area of Science:

Biochemistry
Molecular Biology
Synthetic Biology

Background:

Ribosomes are powerful tools for synthesizing and selecting molecular libraries.
Technologies like phage, yeast, and mRNA display link genotype to phenotype for molecular evolution.
Genetic code expansion is crucial for overcoming ribosome limitations and accessing new materials.

Purpose of the Study:

To review techniques for chemical expansion of genetically encoded libraries.
To discuss the capabilities, limitations, and future opportunities of these techniques.
To cover methods and metrics for assessing modification efficiency and library diversity.

Main Methods:

Review of existing literature on genetic code expansion techniques.
Analysis of methods for synthesizing and selecting molecular libraries.
Discussion of assessment strategies for library modification and diversity.

Main Results:

Chemical genetic code expansion enables the creation of diverse molecular libraries beyond natural amino acid constraints.
Various display technologies effectively couple genotype to phenotype for selecting high-affinity binders.
Established methods exist for evaluating the efficiency and diversity of these expanded libraries.

Conclusions:

Chemical genetic code expansion significantly enhances the scope and utility of molecular library synthesis and selection.
Further development is needed to fully exploit the potential of these techniques for therapeutic target discovery.
Robust assessment methods are vital for ensuring the quality and diversity of genetically expanded libraries.