peptides in chemistry and biology
DESCRIPTION
Peptides in chemistry and biology. Phage display Solid phase peptide synthesis and applications of synthetic libraries Native chemical ligation in protein synthesis. Scott and Smith, Science v. 249 (1990) p. 386. R 1. R 2. R 3. R 4. or. SS. R 1. R 4. R 2. R 3. Fuzeon. - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/1.jpg)
Peptides in chemistry and biology
1. Phage display
2. Solid phase peptide synthesis and applications of synthetic
libraries
3. Native chemical ligation in protein synthesis
![Page 2: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/2.jpg)
R1
R3R2
R4
or
SSR1
R2R3
R4
Scott and Smith, Science v. 249 (1990) p. 386
![Page 3: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/3.jpg)
NH
NNH
HN
O
O
O
NH2
OHS
SH
O QuickTime™ and aAnimation decompressorare needed to see this picture.
NH
N
HN
HN
O
O
O
H2N
O
SSO
QuickTime™ and aAnimation decompressorare needed to see this picture.
![Page 4: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/4.jpg)
NH
N
HN
HN
O
O
O
H2N
O
SSO
NH
N
HN
HN
O
O
O
H2N
O
SSO
![Page 5: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/5.jpg)
![Page 6: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/6.jpg)
![Page 7: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/7.jpg)
![Page 8: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/8.jpg)
QuickTime™ and aTIFF (LZW) decompressor
are needed to see this picture.
Fuzeon
![Page 9: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/9.jpg)
![Page 10: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/10.jpg)
Science v. 271 p. 1854 (1996)
![Page 11: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/11.jpg)
Helical Wheels - to determine amphilphilicity
![Page 12: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/12.jpg)
![Page 13: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/13.jpg)
![Page 14: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/14.jpg)
Native chemical ligation--Steve Kent
![Page 15: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/15.jpg)
![Page 16: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/16.jpg)
![Page 17: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/17.jpg)
100-500 µ 500 nm
Cl
Cl
Cl
Cl
15 Å
Solid phase peptide synthesis
![Page 18: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/18.jpg)
ClOH
O
O
HO
Cs2CO3
O
OOHO
acid-labile linker
= LinkerHO
![Page 19: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/19.jpg)
Fmoc Solid Phase Peptide Synthesis
HN
O
O
HN
O
OH
O
O N
NN
N
Coupling Agent
Fmoc
Fmoc
LinkerO
OH2N
S
LinkerO
OHN
S
O
NH
FmocBase
LinkerO
OHN
S
O
H2N
![Page 20: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/20.jpg)
NH
HNO
OO
Fmoc
NH
NHO
OHO
ONH
X1 HN N
H
HN NH2
O
O
O
OX2
X3
X4
X5
1. Cyclization (Peptide coupling)2. Cleavage (acid)
H2NHN
O
O
OHN
X1
NH
NH
NH
HN
O
O
O
O
X2
X3
X4X5
1. Chain elongation (Fmoc peptide synthesis)
2. Allyl ester deprotection
![Page 21: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/21.jpg)
Gramicidin S - a cyclic peptide antibiotic
![Page 22: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/22.jpg)
Linker
A
B
C
A
Linker
B
Linker
C
Linker
Pool
A
Linker
B
Linker
C
Linker
Split pool synthesis
![Page 23: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/23.jpg)
D
E
F
A
Linker
B
Linker
C
Linker
A
Linker
B
Linker
C
Linker
A
Linker
B
Linker
C
Linker
D D D
E E E
F F F
Split
A
Linker
B
Linker
C
Linker
A B C
A B C
A B C
![Page 24: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/24.jpg)
AXX
Linker
BXX
Linker
CXX
Linker
XDX
Linker
XEX
Linker
XFX
Linker
XXG
Linker
XXH
Linker
XXI
Linker
Most active predicted sequence: BDI
Positional scanning
![Page 25: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/25.jpg)
How to identify kinase substrates?
HO OPOOO
kinase
Signal output
Positional scanning library
![Page 26: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/26.jpg)
Cantley et al. JBC v. 272 (1997) p. 952
O
POO
O
OH
PKC isoforms
![Page 27: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/27.jpg)
OH
N O
FeO
O
O
OH2
OH2
N
O
O
O
OO
O P OO
Wash, sequencebound peptides
![Page 28: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/28.jpg)
Results
![Page 29: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/29.jpg)
Approaches to the study of protein function
1. Biochemistry2. Genetics3. Pharmacology
http://bio.research.ucsc.edu/people/kellogg/
![Page 30: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/30.jpg)
Approaches to the study of protein function
1. Biochemistry - requires cell-free assay
![Page 31: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/31.jpg)
2a. Forward genetics
mutagenize Screen for interesting phenotype
Trace phenoptype to mutation
![Page 32: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/32.jpg)
2b. Reverse genetics
a. Directed deletions, point mutations
b. Gene silencing (siRNA)
c. Knock-out mice
![Page 33: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/33.jpg)
Mayer et al., Science (1999) v. 286 pp. 971 - 974
3a. Forward chemical genetics
![Page 34: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/34.jpg)
control
+ monastrol
![Page 35: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/35.jpg)
http://mc11.mcri.ac.uk/wrongtrousers.html
Kinesin movies
http://www.proweb.org/kinesin/
Target ID: the candidate approach
![Page 36: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/36.jpg)
![Page 37: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/37.jpg)
![Page 38: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/38.jpg)
Reverse Chemical Genetics Kevan ShokatCurr. Op. Chem. Biolv. 5 p. 360 (2001)
![Page 39: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/39.jpg)
![Page 40: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/40.jpg)
![Page 41: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/41.jpg)
![Page 42: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/42.jpg)
![Page 43: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/43.jpg)
![Page 44: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/44.jpg)
![Page 45: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/45.jpg)
![Page 46: Peptides in chemistry and biology](https://reader035.vdocuments.mx/reader035/viewer/2022062322/56814bfd550346895db8fb83/html5/thumbnails/46.jpg)
Ellman, et al.