Non-Canonical Amino Acids in Analyses of Protease Structure and Function
Peter Goettig1, Nikolaj G Koch2,3, Nediljko Budisa3,4
1Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Paracelsus Medical University, Strubergasse 21, 5020 Salzburg, Austria.
International Journal of Molecular Sciences
|September 28, 2023
Summary
Non-canonical amino acids, synthesized chemically or naturally modified, offer protease resistance and are valuable tools for enzyme studies. Their unique properties are driving innovation in drug development and bioimaging applications.
Area of Science:
- Biochemistry
- Chemical Biology
- Drug Discovery
Background:
- Organisms use 20 canonical amino acids for protein synthesis.
- Natural and synthetic non-canonical amino acids have diverse biological roles.
- Non-canonical amino acids offer unique properties like protease resistance.
Purpose of the Study:
- To review recent advancements in protease research utilizing non-canonical amino acids.
- To highlight the potential of non-canonical amino acids in pharmaceutical development.
- To explore applications in enzyme inhibition, kinetics, and bioimaging.
Main Methods:
- Review of current literature on non-canonical amino acids in protease research.
- Analysis of synthetic strategies for creating non-canonical amino acids.
- Examination of applications in drug design and biochemical studies.
Main Results:
- Non-canonical amino acids enhance resistance to proteolytic degradation.
- They serve as effective tools for enzyme specificity profiling and inhibition.
- Bio-orthogonal labeling enables advanced cross-linking and click chemistry for structural studies.
Conclusions:
- Non-canonical amino acids present significant potential for novel protease-activated prodrugs.
- These compounds are advancing pharmaceutical development, with some in clinical trials.
- Further research promises expanded applications in medicine and biotechnology.
Keywords:
bioorthogonal tagsclick chemistrycross-linkinggenetic code expansioninhibitory potencynon-canonical amino acidspharmaceutical compoundprotease specificityproteinogenic amino acidunnatural amino acidMore Related Videos
11:47Residue-specific Incorporation of Noncanonical Amino Acids into Model Proteins Using an Escherichia coli Cell-free Transcription-translation System
Published on: August 1, 2016
16.0K
09:47The Determination of Protease Specificity in Mouse Tissue Extracts by MALDI-TOF Mass Spectrometry: Manipulating PH to Cause Specificity Changes
Published on: May 25, 2018
6.8K
Related Concept Videos
03:42Amino acids
89.2K
Amino acids are the monomers that comprise proteins. Each amino acid has the same fundamental structure, which consists of a central carbon atom, or the alpha (α) carbon, bonded to an amino group (NH2), a carboxyl group (COOH), and to a hydrogen atom. Every amino acid also has another atom or group of atoms bonded to the central atom known as the R group. There are 20 common amino acids present in proteins, each with a different R group. Variation in the amino acid sequence is responsible...
89.2K
01:28What are Proteins?
14.7K
Proteins are polymers of amino acids linked together by peptide bonds. Proteins and polypeptides are interchangeably used to refer to long chains of amino acids. However, polypeptides have a molecular weight of fewer than 10,000 daltons, while proteins have greater molecular weight. Polypeptides with less than 20 amino acids are called oligopeptides or simply peptides. Interactions among the constituent amino acid side chains of proteins help them fold into a stable 3-dimensional...
14.7K
01:24Protein Organization
6.5K
Proteins are polymers of amino acid residues. They are versatile and responsible for different cellular functions, including DNA replication, molecular transport, catalysis, and structural support. Proteins have a hierarchical structure comprising at least three levels of organization: primary, secondary, and tertiary structure. Some large proteins have a quaternary structure where individual protein subunits are linked together.
The primary structure of a protein is its amino acid sequence....
The primary structure of a protein is its amino acid sequence....
6.5K
01:19Allosteric Proteins-ATCase
5.8K
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
5.8K
02:15Protein and Protein Structure
79.7K
Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein's shape is critical to its function. For example, an enzyme...
A protein's shape is critical to its function. For example, an enzyme...
79.7K
01:22Protein Folding
118.4K
Overview
118.4K