Molecular Biology

1. GENETIC CODE
MOLECULAR BIOLOGY
PROJECT
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TABLE OF CONTENTS
INTRODUCTION......................................................................................................................... 3
BACKGROUND: MAKING A PROTEIN ................................................................................ 3
Codons ......................................................................................................................................... 3
Reading frame.............................................................................................................................. 3
DISCOVERY OF THE GENETIC CODE................................................................................. 3
THE CODE IS EVOLVABLE..................................................................................................... 4
UNIVERSALITY OF THE GENETIC CODE AND COLLECTIVE EVOLUTION ........... 5
TYPES OF GENETIC MUTATIONS ........................................................................................ 5
SILENT MUTATIONS AND REDUNDANT CODING........................................................... 5
MISSENSE MUTATION............................................................................................................ 5
NONSENSE MUTATION .......................................................................................................... 6
DELETION.................................................................................................................................. 6
INSERTION ................................................................................................................................ 6
DUPLICATION .......................................................................................................................... 6
FRAMESHIFT MUTATION ...................................................................................................... 6
What does it mean to “change the genetic code? ....................................................................... 7
ENGINEERING EXPANDED GENETIC CODES .................................................................. 7
CODON SUPPRESSION............................................................................................................ 7
CODON REASSIGNMENT ....................................................................................................... 7
CODON CREATION.................................................................................................................. 8
OVERCOMING CHALLENGES IN ENGINEERING THE GENETIC CODE....................... 8
BARRIERS TO CHANGING THE GENETIC CODE ............................................................ 9
BIOCHEMICAL BARRIERS ..................................................................................................... 9
GENETIC BARRIERS................................................................................................................ 9
GENOME ENGINEERING BARRIERS.................................................................................... 9
GENOME ENGINEERING TECHNOLOGIES ....................................................................... 9
GENETIC CODE AND ITS APPLICATION ......................................................................... 10
IN VACCINE DEVELOPMENT............................................................................................. 11
SYNTHETIC BIOLOGY .......................................................................................................... 11
THERAPEUTICS...................................................................................................................... 11
REFRENCES .............................................................................................................................. 12

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INTRODUCTION
Nearly all organisms share a common genetic code, the language that specifies how genetic
information is interpreted to produce proteins.The genetic code links groups of nucleotides in an
mRNA to amino acids in a protein. Start codons, stop codons, reading frame.Decoding messages
is also a key step in gene expression, in which information from a gene is read out to build a
protein Everything in our cells is ultimately built based on the genetic code. Our hereditary
information – that is, the information that’s passed down from parent to child – is stored in the
form of DNA. That DNA is then used to build RNA, proteins, and ultimately cells, tissues, and
organs.
BACKGROUND: MAKING A PROTEIN
Genes that provide instructions for proteins are expressed in a two-step process.
In transcription, the DNA sequence of a gene is "rewritten" in RNA. In eukaryotes, the RNA
must go through additional processing steps to become a messenger RNA, or mRNA.
In translation, the sequence of nucleotides in the mRNA is "translated" into a sequence of amino
acids in a polypeptide (protein chain).
Codon
Cells decode mRNAs by reading their nucleotides in groups of three, called codons. Here are
some features of codons:
 Most codons specify an amino acid.
 Three "stop" codons mark the end of a protein.
 One "start" codon, AUG, marks the beginning of a protein and also encodes the amino
acid methionine.
Reading frame
To reliably get from an mRNA to a protein, we need one more concept: that of reading frame.
Reading frame determines how the mRNA sequence is divided up into codons during translation.
DISCOVERY OF THE GENETIC CODE
In 1961, Francis Crick and colleagues introduced the idea of the codon. However, it was
Marshall Nirenberg and co-workers who deciphered the genetic code. They showed that four
nucleotide bases – A (adenine), U (uracil), G (guanine) and C (cytosine) ─ form codons of
different base combinations that code for all 20 amino acids during protein synthesis.
Nirenberg and German scientist Johann Mathai conducted a series of experiments to explore
protein synthesis using synthetic RNA. They added RNA strands that contained only one of the
four bases (A,G, U or C) base to a "cell free system," and then added radioactively tagged amino
acids.
When RNA consisting only of the base U was added, radioactive measurements indicated the
synthesis of molecules made up of just one single amino acid, which was phenylalanine. This
showed that the triplet made up of bases UUU results in phenylalanine being added to the
polypeptide chain as it grows. In this way, the researchers deciphered 35 codons by year 1963
and more than 60 by 1966.

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University of Wisconsin researcher, HarGobind Khorana built on Nirenberg's work by producing
synthetic RNA molecules with specific nucleotide combinations. Then, in 1965, Robert Holley
of Cornell University elucidated the structure of transfer RNA (tRNA), the molecule involved in
translating RNA, so that a protein can be made. Marshall W. Nirenberg, HarGobind Khorana,
and Robert W. Holley were jointly awarded the 1968 Nobel Prize in Medicine “for their
interpretation of the genetic code and its function in protein synthesis."
THE CODE IS EVOLVABLE:
The code expansion theory proposed in Crick’s seminal paper posits that the actual allocation of
amino acids to codons is mainly accidental and ‘‘yet related amino acids would be expected to
have related codons’’. This concept is known as‘ ‘frozen accident theory’’ because Crick
maintained, following the earlier argument of Hinegardner and Engelberg that, after the
primordial genetic code expanded to incorporate all 20 modern amino acids, any change in the
code would result in multiple, simultaneous changes in protein sequences and,
consequently,would be lethal, hence the universality of the code.
Today, there is ample evidence that the standard code is not literally universal but is prone to
significant modifications, without change to its basic organization.
Three major theories have been suggested to explain the changes in the code. The ‘‘codon
capture theory’’ proposes that, under mutational pressure to decrease genomic GC-content,
some GC-rich codons might disappear from the genome (particularly, a small, e.g., organelle
genome). Then, because of random genetic drift, these codons would reappear and would be
reassigned as a result of mutations in non-cognate tRNAs. This mechanism is essentially neutral,
that is, codon reassignment would occur without generation of aberrant or nonfunctional
proteins.
Another concept of code alteration is the ‘‘ambiguous intermediate’’ theory which posits that
codon reassignment occurs through an intermediate stage where a particular codon is
ambiguously decoded by both the cognate tRNA and a mutant tRNA.
The same mechanism might also apply to reassignment of a stop codon to a sense codon, when a
tRNA that recognizes a stop codon arises by mutation and captures the stop codon from the
cognate release factor. Under the ambiguous intermediate hypothesis, a significant negative
impact on the survival of the organism could be expected.
Finally, evolutionary modifications of the code have been linked to ‘‘genome streamlining’’.
Under this hypothesis, the selective pressure to minimize mitochondrial genomes yields
reassignments of specific codons, in particular, one of the three stop codons.
According to the coevolution theory, there were three main phases of amino acid entry into the
genetic code:
 Phase 1
The first amino acids came from prebiotic synthesis
 Phase 2
Amino acids entered the code by means of biosynthesis from the phase 1 amino acids
 Phase 3
Amino acids are introduced into proteins through posttranslational modifications. Under the
coevolution theory, evolution of metabolic pathways is an important source of new amino acids.
Two major criticisms of the coevolution theory have been put forward. First, the coevolution

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scenario is very sensitive to the choice of amino acid precursor-product pairs, and the choice of
these pairs is far from being straightforward.
UNIVERSALITY OF THE GENETIC CODE AND COLLECTIVE EVOLUTION:
Whether the code reflects biosynthetic pathways according to the coevolution theory or was
shaped by adaptive evolutionary forces to minimize the burden caused by improper translated
proteins or even to maximize the rate of the adaptive evolution of proteins , a fundamental but
often overlooked question is why the code is (almost) universal. Of course, the stereo-chemical
theory, in principle, could offer a simple solution, namely, that the codon assignments in the
standard code are unequivocally dictated by the specific affinity between amino acids and their
cognate codons. The central idea is that universality of the genetic code is a condition for
maintaining the (horizontal) flow of genetic information between communities of primordial
replicators, and this information flow is a condition for the evolution of any complex biological
entities.
TYPES OF GENETIC MUTATIONS
Because the genetic code contains the information to make the stuff of life, errors in an
organism’s DNA can have catastrophic consequences. Errors can happen during DNA
replication if the wrong base pair is added to a DNA strand, if a base is skipped, or if an extra
base is added.
Rarely, these errors may actually be helpful – the “mistaken” version of the DNA may work
better than the original, or have an entirely new function! In that case, the new version may
become more successful, and its carrier may out-compete carriers of the old version in the
population. This spread of new traits throughout a population is how evolution progresses.
SILENT MUTATIONS AND REDUNDANT CODING
In some cases, genetic mutations may not have any effect at all on the end product of a protein.
This is because; most amino acids are connected to more than one codon.
Glycine, for example, is coded for by the codons GGA, GGC, GGG, and GGU. A mutation
resulting in the wrong nucleotide being used for the last letter of the glycine codon then would
make no difference. A codon starting in “GG” would still code for glycine, no matter what letter
was used last.
The use of multiple codons for the same amino acid is thought to be a mechanism evolved over
time to minimize the chance of a small mutation causing problems for an organism.
MISSENSE MUTATION
In a missense mutation, the substitution of one base pair for an incorrect base pair during DNA
replication results in the wrong amino acid being used in a protein.
This may have a small effect on an organism, or a large one – depending on how important the
amino acid is to the function of its protein, and what protein is affected. A missense mutation
may result in an enzyme that almost as well as the normal version – or an enzyme that does not
function at all.

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NONSENSE MUTATION
A nonsense mutation occurs when the incorrect base pair is used during DNA replication – but
where the resulting codon does not code for an incorrect amino acid. Instead, this error creates a
stop codon or another piece of information that is indecipherable to the cell.
As a result, the ribosome stops working on that protein and all subsequent codons are not
transcribed. Nonsense mutations lead to incomplete proteins, which may function very poorly or
not at all.
DELETION
In a deletion mutation, one or more DNA bases are not copied during DNA replication. Deletion
mutations come in a huge range of sizes – a single base pair may be missing, or a large piece of a
chromosome may be missing.
Smaller mutations are not always less harmful. The loss of just one or two bases can result in a
frameshift mutation that impairs a crucial gene. By contrast, larger deletion mutations may be
fatal – or may only result in disability, as in DiGeorge Syndrome and other conditions that result
from the deletion of part of a chromosome.
The reason for this is that DNA is very much like computer source code – one piece of code
might be crucial for the system to turn on at all, while other pieces of code might just ensure that
a website looks pretty or loads quickly. Depending on the function of the piece of code that is
deleted or otherwise mutated, a small change can have catastrophic consequences – or a
seemingly large corruption of code one can result in a system that is just a bit glitch.
INSERTION
An insertion mutation occurs when one or more nucleotides are erroneously added to a growing
DNA strand during DNA replication. On rare occasions, long stretches of DNA may be
incorrectly added in the middle of a gene.
Like a missense mutation, the impact of this can vary. The addition of an unnecessary amino acid
in a protein may make the protein only slightly less efficient; or it may cripple it.
DUPLICATION
A duplication mutation occurs when a segment of DNA is accidentally replicated two or more
times. Like the other mutations listed above, these may have mild effects – or they may be
catastrophic.
FRAMESHIFT MUTATION
A frameshift mutation is a subtype of insertion, deletion, and duplication mutations. In a
frameshift mutation, one or two amino acids are deleted or inserted – resulting in a shifting of the
“frame” which the ribosome uses to tell where one codon stops and the next begins.
This type of error can be especially dangerous because it causes all codons that occur after the
error to be misread. Typically, every amino acid added to the protein after the frameshift
mutation is wrong.

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Imagine if you were reading a book – but at some point during the writing, a programming error
happened such that every subsequent letter shifted one letter later in the alphabet. This is
approximately what happens in a frameshift mutation.
WHAT DOES IT MEAN TO “CHANGE THE GENETIC CODE?
The term “genetic code” has been used with different meanings in different contexts. Since this
can lead to confusion, we propose less ambiguous alternatives for “changing the genetic code.”
1) Changing the genome sequence (e.g., synonymous codon swaps in one or more genes)
will be referred to as genome editing.
2) Introducing new amino acid assignments of one or more codons without removing the
original function (e.g., UAG decoded as both a stop and an amino acid will be referred to
as codon suppression.
3) Changing the amino acid assignments of one or more codons genome wide (e.g., genomic
ally recoded organisms will be referred to as codon reassignment.
4) Adding a new codon to the translation code table (e.g., using quadruplet codons or
codons composed of unnatural bases will be referred to as codon creation. Broadly
speaking, the term “genetic code” will be used throughout this review to describe the
codon assignments in the translation code table. Codon suppression, reassignment, and
creation are all ways of changing a genetic code.
ENGINEERING EXPANDED GENETIC CODES
In vitro translation systems offer the ultimate flexibility to implement alternate genetic codes.
Since translation components can be prepared separately, non-specific amino-acylation methods
such as CA ligation and flexizyme can be used to incorporate a broad selection of non-standard
amino acids (nsAAs). As a result, in vitro translation has been the best way to produce unnatural
backbones for synthetic non ribosomal peptide mimetics and polymer materials. Furthermore,
the production of ribosomes in vitro may accommodate extensive modifications that could
otherwise compromise fitness in vivo. Recent reports of orthogonal 16S rRNA, orthogonal
tRNAs, tethering 16S to 23S rRNA, provide the infrastructure to evolve ribosomes with radically
modified functions.
CODON SUPPRESSION
In vivo systems are well-suited for inexpensive, simple, and scalable translation using nsAAs,
but must be compatible with essential cellular processes. While sense codons have been
transiently diverted to incorporate diverse nsAAs by metabolic labeling, persistent metabolic
labeling is likely to be highly deleterious. Even evolving tolerance for structurally similar Trp
analogs has met varying success in different systems. In contrast, ambiguous decoding of stop
codons is well-tolerated in E. coli, making it possible to introduce orthogonal translation
machinery capable of producing high yields of nsAA-containing proteins in vivo. The
implementation of orthogonal translation machinery has led to an explosion in the number of
nsAAs (currently more than 167 nsAAs) that can be site-specifically incorporated into proteins
for applications in medicine and bioremediation
CODON REASSIGNMENT
While ambiguous decoding has long made it possible to produce nsAA-containing proteins, only
recently has the translation function of a codon been unambiguously reassigned, enabling the

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sustained expression of proteins containing one or more nsAAs. While a surprisingly small
number of changes permit the disruption of UAG termination, the remaining natural UAG
codons provide a selective pressure for efficient UAG translation. This destabilizes the genetic
code by selecting for spontaneous suppressor mutations that incorporate canonical amino acids at
UAG codons. This strategy could prove even more problematic for sense codon reassignment,
since stop codons only occur once at the end of genes, limiting the impact of codon reassignment
on the proteome. Therefore, the most general strategy to expand the genetic code using
reassigned codons involves
 Identifying all genomic instances of a target codon
 Replacing them with synonymous codons
 Abolishing the target codon’s natural function by inactivating its translation factors
 Introducing new translation function by integrating orthogonal translation systems
 Introducing new instances of the target codon to specifically and efficiently incorporate
nsAAs into desired proteins
Using this strategy, expanded genetic codes can be stabilized by redesigning essential proteins to
functionally depend on a specific nsAA for survival. However, it remains a major biochemical,
genetic, and technical challenge to reassign codons that are commonly utilized throughout a
genome.
CODON CREATION
Beyond repurposing one or more of the existing 64 codons, it may be possible to add a new base
pair or to engineer quadruplet or quintuplet genetic codes, which could give 63 = 216, 44 = 256,
or 54 = 625 codons, respectively. Indeed, exciting progress has hinted at the promise of creating
new codons, which would need to be replicated, transcribed, and translated. Several unnatural
base pairs exhibiting high fidelity replication by PCR and compatibility with proofreading
mechanisms of Exo+ polymerases have been developed. Additionally, transcription (using T7
RNA polymerase) and reverse transcription have been demonstrated. Finally, codons containing
unnatural base pairs have been implemented to translate peptides containing unnatural amino
acids using an E. coli-derived in vitro translation system. This means that codons containing
unnatural base pairs can be immediately implemented for in vitro translation of proteins
OVERCOMING CHALLENGES IN ENGINEERING THE GENETIC CODE
Why has the genetic code been so refractory to change? While it is possible that more divergent
genetic codes have yet to be discovered, several factors help to conserve the genetic code.
Evolution tends to increase biological complexity; leading to the large genomes of modern free-
living organisms (the smallest known genome with a full complement of essential genes has
580,070 base pairs encoding 470 predicted open reading frames. With a few exceptions, these
organisms use all 64 codons to encode their proteins while simultaneously accommodating
overlapping sequence features such as protein binding sites, promoters, splicing signals, and
RNA secondary structure. In this context, the genetic code provides fundamental biochemical
constraints that guide how a genome is put together. Therefore, the genetic code shapes how
mutations affect an evolving genome, while the genome relies on a stable genetic code to
faithfully produce proteins essential for life. Any change in codon function must be tolerated at
all instances genome-wide. Therefore small changes in the genetic code must be accompanied by
many compensatory changes in the rest of the genome. This scenario is unlikely to occur by

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random mutagenesis, but current genome engineering technologies are now making it possible to
rationally change the genetic code.
BARRIERS TO CHANGING THE GENETIC CODE
BIOCHEMICAL BARRIERS
Ribosomes translate proteins by adding an amino acid to the nascent polypeptide in response to
three-nucleotide codons on messenger RNAs (mRNAs). The identity of the amino acid is
controlled at multiple discrete steps. First, aminoacyl-tRNA synthetases (aaRSs) charge transfer
RNAs (tRNAs) with their correct amino acids. The aminoacyl-tRNA is then shuttled into the
active site of the ribosome by elongation factor Tu (EF-Tu), where base pairing between the
mRNA codon and tRNA anticodon allows transfer of the amino acid onto the nascent peptide
chain regardless of the amino acid identity. Translation involves more than 100 proteins and
RNAs, a subset of which have been engineered to expand the genetic code. Together with
insights from natural non-canonical genetic codes, this work suggests that the biochemistry of
the genetic code is remarkably flexible.
GENETIC BARRIERS
Despite the impressive biochemical flexibility of the genetic code, our inadequate understanding
of how to design genomes remains a major barrier for creating organisms with radically new
genetic codes. Even in the age of chemically synthesized chromosomes, genomes must be
designed based on incomplete information, and even the best-annotated genomes remain
incompletely understood at all levels of complexity from single nucleotide variants to genome
architecture.
GENOME ENGINEERING BARRIERS
Despite much progress, it remains difficult to predict the correct changes to make at every level
of genome complexity from single nucleotide changes to megabase/gigabase genome
construction. Accepting the fact that existing information is inadequate, draft genomes must be a
best guess based on as much information as possible.
Given our tenuous understanding of how to design genomes, effective genome engineering
technologies must integrate the information that is known, and overcome the inevitable design
flaws that will arise based on our incomplete knowledge. We know that all natural instances of a
codon must be removed from the genome in order to abolish its natural translation function. We
know that orthogonal tRNA pairs can introduce new translation functions. We know that we can
stabilize an expanded genetic code by establishing functional dependence on an unnatural amino
acid. The challenge is to produce such genomes by making hundreds or thousands of changes
without introducing any lethal design flaws.
GENOME ENGINEERING TECHNOLOGIES
Engineering the genetic code requires extensive genome manipulation that can affect fitness in
unpredictable ways. With this in mind, we have developed multiplex automated genome
engineering (MAGE) and conjugative assembly genome engineering (CAGE) for rapidly
prototyping and manufacturing genotypes in vivo. MAGE uses the λ bacteriophage β
recombinase and ssDNA oligonucleotides to simultaneously introduce multiple defined
mutations at multiple locations throughout a replicating bacterial genome. Meanwhile, CAGE
uses bacterial conjugation to precisely transfer up to several million base pairs of contiguous
DNA, allowing the production of extensively modified genomes from small segments that are

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easily prototyped in parallel using MAGE. Together, MAGE and CAGE exploit evolution to
combinatorically explore a broad pool of synthetically defined genotypes in vivo, allowing
natural selection to remove deleterious design flaws from the population.
MAGE and CAGE were used to remove all 321 known instances of the UAG codon from E. coli
at a fraction of the predicted cost for genome synthesis. Still, DNA synthesis can be invaluable
for extensively modifying genome sequences, provided that the synthetic genome fragments are
small enough for efficient troubleshooting. For instance, we tested 6496 total mutations across
42 essential genes using inexpensive, chip-based DNA synthesis. Because we tested each
essential gene individually, design flaws could be rapidly mapped and overcome using MAGE.
A similar strategy has been successful for the synthetic yeast 2.0 project and could be extended
to diverse organisms using an ever-growing arsenal of powerful genome engineering tools.
As genome designs increase in complexity, integrated analysis strategies will become essential
for monitoring design clashes, managing genome builds, and analyzing genotypes. There are
many useful genome engineering design and analysis tools available: searchable genome
annotation databases, sequence manipulation and synthetic circuit design tools, sequencing
analysis tools for single nucleotide variants and structural variants, and computational models of
whole organisms. Integrating these design and analysis tools into a cohesive and efficient
software platform will greatly benefit efforts to produce GROs with radically altered genetic
codes.
While more than 167 nAAs have already vastly expanded protein function, radically different
genetic codes will be required to achieve virus resistance, genetic isolation, and stable expansion
of the genetic code. Thirteen out of thirteen codons tested have already shown promise for
reassignment. To implement radically expanded genetic codes, a mechanistic understanding of
biochemical principles will be crucial to engineer orthogonal translation machinery that is
capable of reassigning such sense codons. Additionally, genome engineering methods capable of
interrogating genetic landscapes containing thousands of potentially deleterious changes will be
crucial for producing organisms with reassigned sense codons. Advances in understanding codon
usage, gene function, operon structure, and genome architecture will help establish better
guidelines for genome design, but diversity will remain a crucial aspect in prototyping genomes
with new and useful biological functions.
GENETIC CODE AND ITS APPLICATION
As the fundamental element of inheritance information, the uncovery of secret of genetic code
must play important roles either in theoretical research or practical application for human to
deeply understand the essence of life. At present, the emphasis of genetic code research has been
transferred from code decoding and discovery of codons with particularity characteristics to
investigating its origination, evolution and expansion etc.
The origination and evolution study of genetic code is known as one of the hottest points in
genomics research. As for this issue, many theories and hypothesis have been put forward,
however no material progresses are made up to date.
On the other hand, the redefinition of nonsense codons and expansion study of genetic code have
greatly enriched and developed the primary scientific meanings of genetic code, which
significantly promotes the development of life science research. In this paper, the recent
progresses made with respect to polymorphism, origination, evolution, redefinition of nonsense
codons and expansion studies on genetic code were reviewed, and its potential application values

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were discussed also. This information would be very useful for further applying the results of
genetic code research to the studies in the fields of genomics, medicine etc.
APPLICATION OF GENETIC CODE EXPANSION IN VACCINE DEVELOPMENT
Therapeutic and preventive vaccines are important bio-products that help develop immunity
against particular diseases. The scientific community has spent decades trying to develop
therapeutic vaccines to cure various cancers. However, little progress has been made until now in
the development of therapeutic vaccine partially due to the complexity of human immune
system.
Conversely, preventive vaccines have achieved great success in preventing a variety of diseases,
such as polio, measles, and tetanus. However, key hurdles still exist that hinder developing
efficient and safe vaccines for other diseases, such as AIDS. Since previous efforts have not
provided solutions for some irremediable diseases, novel vaccine strategies are urgently needed.
Genetic code expansion has shown great potential in vaccine development. First, it offers a
simple and effective method to increase immunogenicity of therapeutic vaccines. Second, it
provides a useful tool for generating virus like-particles or conditionally-replicated live viruses
that can be used as preventive vaccines.
SYNTHETIC BIOLOGY
Our canonical 20 amino acids are clearly more than sufficient to support our existence. However,
our ability to manipulate the biological and physicochemical properties of proteins may confer
several advantages, especially from an evolutionary standpoint.
UAAs can be rationally exploited to investigate and perhaps even remedy biological problems
that involve proteins. To this end, UAAs open the door to engineering an extensive range of
chemical, electrical and structural properties that may prove otherwise very challenging and/or
non-existent in the common 20 amino acids. Adding chemically reactive groups to UAAs can
allow them to function as bio-orthogonal handles for specific sites in vitro. In addition to this,
they may be able to function as intracellular protein modifiers and can be used to directly
introduce novel or enhanced catalytic properties to proteins.
UAAs may also be used as heavy atoms for determining the structure of X-rays, redox-active
reagents and probes of hydrogen bonding as well as interactions in proteins.
THERAPEUTICS
UAAs may be widely used for therapeutic purposes - they are particularly useful in cases where
large quantities of a modified protein are required for production. For instance, immunogenic
amino acids may be used to generate vaccines against self-proteins by the breakdown of
immunological tolerance in conditions, such as inflammation or cancer.
UAAs can also be used to generate vaccines against the conserved epitopes of diseases like HIV
and malaria, which are fairly difficult to target with our traditional vaccines.

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