Class notes
Complete syllabus of Chemical Biology MOL-NWI418
- Course
- Institution
With 120 pages of content, this syllabus gives you a handy all-in-one overview of the discussed contents during Chemical Biology.
[Show more]
Seller
Followkeekeevolley
Reviews received
Content preview
By Kayleigh SchourenSummary Chemical Biology
TABLE OF CONTENTS
Introduction ................................................................................................................................. 4
Carbohydrate Synthesis ................................................................................................................ 5
Nomenclature ..................................................................................................................................... 6
Fischer projection rules....................................................................................................................... 7
The anomeric effect ............................................................................................................................ 8
Ring conformations ............................................................................................................................. 9
Protecting groups................................................................................................................................ 9
Ethers ................................................................................................................................................ 10
Acetal / Ketal ..................................................................................................................................... 13
Carbonates ........................................................................................................................................ 13
Amine protecting groups .................................................................................................................. 14
Protecting the anomeric centre ........................................................................................................ 16
Relative reactivity of sugar alcohols ................................................................................................. 17
Regioselective deprotection ............................................................................................................. 21
Functionalization of monosaccharides ............................................................................................. 22
Halogenation ..................................................................................................................................... 22
Inverse the stereochemistry of alcohols ........................................................................................... 23
What to do with the modified/halogenated sugars? ....................................................................... 24
Glycosyl epoxides: ............................................................................................................................. 25
Oligosaccharide Synthesis .......................................................................................................... 27
Anomeric leaving groups .................................................................................................................. 27
Stereochemistry of the glycosidic bond............................................................................................ 30
Glycosidic linkages ............................................................................................................................ 34
Solvent participation ......................................................................................................................... 35
Peptide Synthesis....................................................................................................................... 41
Nomenclature ................................................................................................................................... 41
Peptide Protecting Groups................................................................................................................ 42
Nα amino protection ......................................................................................................................... 43
Cα carboxy protection ....................................................................................................................... 44
Orthogonality .................................................................................................................................... 47
1
, By Kayleigh Schouren
Solution Phase Peptide Chemistry .................................................................................................... 48
carbodiimides.................................................................................................................................... 48
Phosphonium reagents ..................................................................................................................... 49
Uranium reagents ............................................................................................................................. 49
Racemization..................................................................................................................................... 49
Solid Phase Peptide Synthesis........................................................................................................... 50
Peptide Ligations ............................................................................................................................... 54
Larger proteins .................................................................................................................................. 54
Native Chemical Ligation .................................................................................................................. 54
Nature’s ligation................................................................................................................................ 56
Non-native chemical ligation ............................................................................................................ 57
Peptide Modifications ....................................................................................................................... 58
Cyclization ......................................................................................................................................... 58
Disulphide bonds .............................................................................................................................. 59
Labels and tags .................................................................................................................................. 59
Phosphorylation ................................................................................................................................ 59
Close analogues: ............................................................................................................................... 60
PNA ................................................................................................................................................... 61
Synthesis of Oligonucleotides ..................................................................................................... 61
Molecular Structure of Oligonucleotides.......................................................................................... 62
Phosphoramidite coupling ................................................................................................................ 62
Side reactions .................................................................................................................................... 65
Synthesis of RNA ............................................................................................................................... 65
Common modifications ..................................................................................................................... 66
DNA-peptide conjugates ................................................................................................................... 67
Bioorthogonal Chemistry ........................................................................................................... 69
Fluorescent proteins ......................................................................................................................... 69
Metabolic labelling............................................................................................................................ 69
Staudinger Ligation ........................................................................................................................... 70
CuAAC (Huisgen 3+2 dipolar cycloaddition) ..................................................................................... 71
SPAAC (strain-promoted alkyne-azide click ...................................................................................... 71
Tetrazine ligation .............................................................................................................................. 73
Orthogonal bioorthogonal reactions ................................................................................................ 73
Click to release .................................................................................................................................. 73
Protein Engineering : Incorporation of Unnatural Amino Acids .................................................... 74
Method 1: residue specific replacement .......................................................................................... 75
2
, By Kayleigh Schouren
Method 2: site specific incorporation of a 21st amino acid .............................................................. 76
Orthogonal tRNA............................................................................................................................... 77
Expanding the genetic code to 4-letter codons ................................................................................ 80
Protein Engineering : (Semi)Synthetic Protein Modification ........................................................ 82
Adding modified cofactors ................................................................................................................ 84
Use the functionality of protein splicing: .......................................................................................... 85
Enzyme tagging (fusion proteins) ..................................................................................................... 87
Post Translational Modifications (PTMs) ..................................................................................... 88
Phosphorylation ................................................................................................................................ 89
Acetylation ........................................................................................................................................ 91
Methylation....................................................................................................................................... 93
Chemical Glycobiology ............................................................................................................... 95
Glycan labelling ................................................................................................................................. 95
Functional modifications................................................................................................................... 99
Enzymatic labelling ......................................................................................................................... 101
Inhibitors ......................................................................................................................................... 102
Make probes for recycling enzymes ............................................................................................... 104
Glycoprotein synthesis .................................................................................................................... 104
Activity Based Protein Profiling ................................................................................................ 106
Covalent catalysis ............................................................................................................................ 107
Non-covalent catalysis .................................................................................................................... 108
Reactive Cysteine/Lysine profiling .................................................................................................. 109
Cysteine cathepsins in cancer ......................................................................................................... 110
Regulation of Protein Levels ..................................................................................................... 112
DNA modifying techniques ............................................................................................................. 115
Hijack the ubiquitin proteasome system ........................................................................................ 116
Chemical Biology of Oligonucleotides ....................................................................................... 117
Nucleic acid Templated Chemistry ................................................................................................. 118
Expanded genetic alphabet ............................................................................................................ 119
Fluorescent RNA aptamers ............................................................................................................. 120
RNA Structure Profiling ................................................................................................................... 120
Metabolic labelling of DNA ............................................................................................................. 120
3
, By Kayleigh Schouren
INTRODUCTION
What is chemical biology?
‘ use of chemistry to advance a molecular understanding of biology and the harnessing of biology to
advance chemistry’
It is a relatively new field in which the synthesis of the biomolecules is crucial to study their function.
The central dogma on its own cannot explain life, for that we need to understand epigenetics and
post translational modifications (PTM) as well (ubiquitination, cleavage, phosphorylation etc.).
Reversible PTMs are installed by enzymes, whereas irreversible PTMs stem from environmental
factors. PTMs are often specific for amino acids →
Functions of PTMs include regulation of:
- protein maturation
- enzymatic activity
- cellular localization
- stability / turnover
- interactions with other molecules
The most complex PTM is glycosylation, for which
no direct blueprint is available. Glycans can
be N-linked (Arg) and O-linked (Ser or Thr).
50% of all proteins are glycosylated, 90%
of extracellular proteins are glycosylated.
N-glycan biosynthesis starts in the ER
lumen with GlcNAc, Mannose and
eventually Glucose. When proteins are
misfolded and remain in the ER lumen,
their glycan chain will degrade. This is
recognized which leads to elimination by
the ER-associated degradation pathway
(ERAD). The glycan processing continues in
the Golgi. From where proteins will go to
lysosomes or the extracellular
environment.
4
The benefits of buying summaries with Stuvia:
Guaranteed quality through customer reviews
Stuvia customers have reviewed more than 700,000 summaries. This how you know that you are buying the best documents.
Quick and easy check-out
You can quickly pay through credit card or Stuvia-credit for the summaries. There is no membership needed.
Focus on what matters
Your fellow students write the study notes themselves, which is why the documents are always reliable and up-to-date. This ensures you quickly get to the core!
Frequently asked questions
What do I get when I buy this document?
You get a PDF, available immediately after your purchase. The purchased document is accessible anytime, anywhere and indefinitely through your profile.
Satisfaction guarantee: how does it work?
Our satisfaction guarantee ensures that you always find a study document that suits you well. You fill out a form, and our customer service team takes care of the rest.
Who am I buying these notes from?
Stuvia is a marketplace, so you are not buying this document from us, but from seller keekeevolley. Stuvia facilitates payment to the seller.
Will I be stuck with a subscription?
No, you only buy these notes for $5.99. You're not tied to anything after your purchase.
Can Stuvia be trusted?
4.6 stars on Google & Trustpilot (+1000 reviews)
75759 documents were sold in the last 30 days
Founded in 2010, the go-to place to buy study notes for 14 years now