BASICS OF BIOORTHONGONAL CHEMISTRY, ITS HISTORY AND BASIC REACTIONS AND ITS IMPORTANCE ARE COVERED IN THIS PPT

1. BIOORTHOGONAL
CHEMISTRY
Introduction and
Applications
PRESENTED BY
AYUSHJAIN
PALB7286
Dept. of Plant Biotechnology

2. CONTENTS
What is Bioorthogonal Chemistry ???
What is the Purpose of this ???
What are the requirements of Bioorthogonality ???
What’s there in the History ???
What are steps in Bioorthogonal reaction development ??
What are the types of Bioorthogonal Transformations ???
What are its Applications & Future Directions ???
17 JAN 2018AYUSH JAIN, DEPT. OF PLANT BIOTECHNOLOGY, BASIC BIOCHEMISTRY (BCM.501) 2

3. What is
Bioorthogonal
Chemistry
???
The term was coined
by Carolyn R. Bertozzi in
2003
17 JAN 2018AYUSH JAIN, DEPT. OF PLANT BIOTECHNOLOGY, BASIC BIOCHEMISTRY (BCM.501) 3

4. The term Bioorthogonal
chemistry refers to
any chemical
reaction that can occur
inside of living
systems without
interfering with native
biochemical processes
or
Chemical reactions that
neither interact with nor
interfere with a
biological system.
17 JAN 2018AYUSH JAIN, DEPT. OF PLANT BIOTECHNOLOGY, BASIC BIOCHEMISTRY (BCM.501) 4

5. What is the
Purpose of
this ???
Fishing for Selectivity
in a Sea of
Functionality
17 JAN 2018AYUSH JAIN, DEPT. OF PLANT BIOTECHNOLOGY, BASIC BIOCHEMISTRY (BCM.501) 5

6. • Chemist design reactions for a particular Complex target product. “But what if
the challenge [of synthesis] was inverted, wherein the target structure was
relatively simple but the environment in which the necessary reactions must
proceed was so chemically complex and uncontrollable that no two functional
groups could combine reliably and selectively under such conditions?”
– Carolyn R. Bertozzi.
• To Develop Specific tools that can be used for Investigating the Dynamics and
function of Biomolecules in the living system (Interrogate biomolecules).
• Allows for more efficient and non-toxic drug delivery, biological imaging, and
material science.
AYUSH JAIN, DEPT. OF PLANT BIOTECHNOLOGY, BASIC BIOCHEMISTRY (BCM.501) 17 JAN 2018 6
Cell Cell Cell

7. What are the
requirements of
Bio-
Orthogonality
???
AYUSH JAIN, DEPT. OF PLANT BIOTECHNOLOGY, BASIC BIOCHEMISTRY (BCM.501) 17 JAN 2018 7

8. AYUSH JAIN, DEPT. OF PLANT BIOTECHNOLOGY, BASIC BIOCHEMISTRY (BCM.501) 17 JAN 2018 8
Functional
groups used
must be inert to
biological
moieties.
FG’s must be
selective for one
another, Thermo-
dynamically And
Metabolically
stable and
nontoxic to
organisms
Reaction must
work in
biological media
Must have very
fast kinetics,
particularly at
low
concentrations
and in
physiological
Conditions
Reactions leads
to stable
Co-valent
Linkages with
No by products

9. What’s there
in the
History??
AYUSH JAIN, DEPT. OF PLANT BIOTECHNOLOGY, BASIC BIOCHEMISTRY (BCM.501) 17 JAN 2018 9
Green fluorescent proteins are also
quasi-biorthogonal but only for some
specific proteins.

10. • Chemists for a long time struggled to find out
reactions which can full fill all the criteria's of
Bioorthongonality.
• Natural reactions closest to the concept where
condensation reactions of Aldehydes or ketones
with Hydrazides and aminooxy compounds,
which founded use in many bioconjugation
applications in late 1900s.But never achieved
highest level of Bioorthongonality.
• In year 2000 invention of Bioorthogonal
reactions involving functionalities that are not
found in nature took place. Roger Tisen & etal.
Reported bisarsenical/tetracystine reaction.
This made other chemists realize, that through
careful design and tuning of reaction partners
Bioorthongonality can be achieved.
AYUSH JAIN, DEPT. OF PLANT BIOTECHNOLOGY, BASIC BIOCHEMISTRY (BCM.501) 17 JAN 2018 10

11. • The 1st perfect Bioorthogonal reaction were
reactions of azide (a small functional group
that is biostable and can behave as soft
electrophile or as a 1,3-dipole, two modes of
reactivity that are rare in nature).
• Azide debuted as a partner in the
Staudinger ligation with specially tailored
phosphine reagents and then in more
Biofriendly Cu-free Cycloaddition
(A paragon of click chemistry).
• Creative metabolic and genetic engineering
have made it possible to incorporate azides,
alkynes into proteins, glycans, nucleic
acids, lipids, metabolites, and various
PTM’s in cultured and live organisms. The
Bioorthogonal functional group serves as a
chemical reporter.
AYUSH JAIN, DEPT. OF PLANT BIOTECHNOLOGY, BASIC BIOCHEMISTRY (BCM.501) 17 JAN 2018 11

12. What are steps in
Bioorthogonal
reaction
development ??
Remember! All this is
done to meet the
stringent requirements
of rate, selectively and
Biocompatibility
AYUSH JAIN, DEPT. OF PLANT BIOTECHNOLOGY, BASIC BIOCHEMISTRY (BCM.501) 17 JAN 2018 12

13. Identification or invention of a highly specific ligation process
that works well in water.
Problems associated with reactant/product stabilities and
reaction biocompatibility is anticipated and addressed.
The reaction is first optimized “in the flask” where the
fundamental scope, limitations and mechanistic
modifications are explored.
The reaction is then tested in variety of biological
environments.
The most optimized transformations are then tested and
employed in living organisms and animals.
AYUSH JAIN, DEPT. OF PLANT BIOTECHNOLOGY, BASIC BIOCHEMISTRY (BCM.501) 17 JAN 2018 13

14. What are the
types of
Bioorthogonal
Transformations
???
AYUSH JAIN, DEPT. OF PLANT BIOTECHNOLOGY, BASIC BIOCHEMISTRY (BCM.501) 17 JAN 2018 14

15. AYUSH JAIN, DEPT. OF PLANT BIOTECHNOLOGY, BASIC BIOCHEMISTRY (BCM.501) 17 JAN 2018 15

16. AYUSH JAIN, DEPT. OF PLANT BIOTECHNOLOGY, BASIC BIOCHEMISTRY (BCM.501) 17 JAN 2018 16

17. AYUSH JAIN, DEPT. OF PLANT BIOTECHNOLOGY, BASIC BIOCHEMISTRY (BCM.501) 17 JAN 2018 17

18. AYUSH JAIN, DEPT. OF PLANT BIOTECHNOLOGY, BASIC BIOCHEMISTRY (BCM.501) 17 JAN 2018 18

19. AYUSH JAIN, DEPT. OF PLANT BIOTECHNOLOGY, BASIC BIOCHEMISTRY (BCM.501) 17 JAN 2018 19

20. AYUSH JAIN, DEPT. OF PLANT BIOTECHNOLOGY, BASIC BIOCHEMISTRY (BCM.501) 17 JAN 2018 20

21. AYUSH JAIN, DEPT. OF PLANT BIOTECHNOLOGY, BASIC BIOCHEMISTRY (BCM.501) 17 JAN 2018 21

22. AYUSH JAIN, DEPT. OF PLANT BIOTECHNOLOGY, BASIC BIOCHEMISTRY (BCM.501) 17 JAN 2018 22

23. What are its
Applications &
Future
Directions ???
AYUSH JAIN, DEPT. OF PLANT BIOTECHNOLOGY, BASIC BIOCHEMISTRY (BCM.501) 17 JAN 2018 23
We choose to Dance with the
Dazzling molecular and
functional complexity of
evolution, without stepping on
Nature’s Toes.

24. AYUSH JAIN, DEPT. OF PLANT BIOTECHNOLOGY, BASIC BIOCHEMISTRY (BCM.501) 17 JAN 2018 24
In Protein
Bioconjugations
powerful tool for
the exploration of
protein expression,
localization and
function in their
native environment
In Nucleic Acids
Bioconjugations
For studying
nucleic acids in their
native environment.
In Glycan
Bioconjugations
Probing the dynamic
changes of glycan is
of great importance
for investigating
glycobiology and
improving disease
diagnosis and
therapeutics In Lipids
Bioconjugations
Direct imaging of
phospholipid &
other lipids
synthesis, turnover
& their localization
inside cells

25. AYUSH JAIN, DEPT. OF PLANT BIOTECHNOLOGY, BASIC BIOCHEMISTRY (BCM.501) 17 JAN 2018 25
Need for more
reactions that
can be orthogonal
to one another
Group 15 has
been huge
contributor to
this field, so
perhaps
Sb(Antimony) or
Bi(Bismuth)
could work as
well.
Use of
ultrasound and
other
biocompatible
energy forms to
increase reaction
rates
Some natural
biomolecules can
be engineered to
possess “latent
Bioorthogonality”

26. BIBLIOGRAPHY
• Carolyn R. Bertozzi (2011), “A Decade of Bioorthogonal Chemistry”, Acc. Chem Res., Vol
44(9):651-653.
• Craig S. McKay and M.G. Finn (2014), “Click Chemistry in Complex Mixtures
Bioorthogonal Bioconjugation”, J. Chembiol., Vol 21:1075-1101.
• Mengmeng Zheng, Li Zheng, Peiyuan Zhang, Jinbo Li and Yan Zhang (2015)
“Development of Bioorthogonal Reactions and Their Applications in Bioconjugation”,
Journal Molecules, Vol 20 :3190-3205.
• Ellen M. Sletten and Carolyn R. Bertozzi(2009),“Bioorthogonal Chemistry: Fishing for
Selectivity in a Sea of Functionality”, Angew Chem Int Ed Engl.,48(38): 6974–6998.
• “Bioorthogonal Chemistry”, Rachel Whittaker, February 13, 2013, Wednesday
Literature Talk.
• “Bioorthogonal Chemistry”, A. Manos-Turvey, Wipt Group: Frontiers of Chemistry, Jan
17,2015.
AYUSH JAIN, DEPT. OF PLANT BIOTECHNOLOGY, BASIC BIOCHEMISTRY (BCM.501) 17 JAN 2018 26

27. A Tribute to
Molecular
Biologist of all
time on his 96th
Birthday on
January 17, 2018
• He Deciphered the Genetic Code
• 1968 Nobel Prize for Physiology
or Medicine.
• Dr. Har Gobind Khorana
17 JAN 2018 27