첨단화학의 이해 synthesis make me a molecule biology materials chemistry
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첨단화학의 이해Synthesis
Make me a molecule
Biology Materials
Chemistry
첨단화학의 이해DNA, Genes, and Proteins
첨단화학의 이해Genomics, Proteomics and Chemical Genetics
Genomics
Proteomics Chemical Genetics
Gene Sequence:- ~30,000 genes- unable to identify therapeutic targets- no protein function and disease relevance
Protein Function: - purification and structure determination- ~100,000 proteins in human - 75% no known cellular functions
Small Molecules: - modulate biological functions of proteins
ControlBiologicalFunctions
Drug Drug DiscoveDiscove
ryry
첨단화학의 이해
proteinnormalsignal activateactivate
protein functionprotein function
deactivatedeactivateprotein functionprotein function
falsesignal
Protein Function (Drug Action)
첨단화학의 이해
N
HNN
N
N
N
O
O
Viagra
(treatment of impotence)
N
N
CO2Et
Cl
Claritin(antihistamine,i.e. antiallergic)
NH
N
O
OH
S NHO
HO
H
H
Viracept
(treatment of AIDS)
NH
O
OO
F
Paxil
(psychotherapeutic)
F3C O NH
Prozac(antidepressant)
NHS
O
HO2C
Captopril
(treatment of hypertension)
N
N N
N
O
H2N
OHO
Acyclovir(antiviral)
N
N
Cl
O
Valium(tranquilizer)
HN OPt
O O
H2N NH2
Carboplatin
(treatment of ovarian cancer)
O
O
NMe2
NH2
Novocain
(local anesthetic)
Selected Medications of 20th Century
NH2
ClCl
Zoloft
(psychotherapeutic)
N
HN
S N
MeO
O
OMe
Prilosec
(antispasmodic)
OS
HN
N
NO2
HN
Zantac(treatment of ulcer)
N
HN
SNH
NH
NCN
Tagamet(treatment of ulcer)
첨단화학의 이해
HO
H
OH
H H
O
H
OH
H H
H
17-ethynylstradiol norethindrone
(the "Pill"; contraceptive)
O
O
OHHO OMe
O
O
O
HON
OMe
OH
Clarithromycin(antibacterial)
N
S
HOO
O
H H
CO2H
NH2
Ampicillin(antibiotic)
NO
H
CO2H
OH
Clavulanic acid(-lactamase inhibitor)
Augmentin(antibiotic)
Selected Medications of 20th Century
O
HO
RO
N
R= H MorphineR= Me Cocaine
(pain killer)
OO
O
OH
OH
R H
R= HR=Me
MevacorZocor
(treatment of high cholesterol)
첨단화학의 이해Target-Oriented Organic Synthesis
Known active sitesof target proteins
Design and synthesisof target molecules
biological effects
첨단화학의 이해
정상
이상
Diversity-Oriented Organic Synthesis
Library of diverse small molecules
unknown proteins
첨단화학의 이해
Combinatorial ChemistryCombinatorial Chemistry
첨단화학의 이해
44 = 256 개 tetramer
Combinatorial Library
4 개의 monomer
••••
Nn Combinations
첨단화학의 이해
resin +monomer
shakeresin
cleavage
wash
Solid Phase Synthesis 의 기본원리
wash
첨단화학의 이해Solid-Phase Synthesis of Peptides
polymerbead
amino acid
cleave
In 1960s, Bruce Merrifield: peptide synthesis from amino acids
peptide
첨단화학의 이해Solid Phase Library Synthesis
• polymer supported synthesis: easy purification
• fast generation of diverse library of molecules in few steps
• limited reactions compared to solution reactions
Split-Mix (split-pool) synthesis
Parallel synthesis
첨단화학의 이해Split-Mix Process
Mix-SplitCouple
Mix-SplitCouple
33= 27tag each bead!
첨단화학의 이해Parallel synthesis
- synthesis of small number of focused library
- no tagging beads!
첨단화학의 이해Solid Phase Library
203 = 8000 tripeptides
20 amino acids
202 = 400 dipeptides
204 = 160,000 tetrapeptides
In 1991s, Houghten & Lam: synthesis of a huge peptide library
peptide
DNA: fully automatic (solution)
Solid-phase synthesis
ln 1992, Jon Ellman: synthesis of non-peptide drug-like molecules by solid phase synthesis
carbohydrate
small molecule (drug-like)
첨단화학의 이해
2,180,106 compounds
Combination of Chemical Building Blocks
첨단화학의 이해Virtual Library
virtual library: computer simulated fitting of virtual molecules with the active site of the target enzyme
Novel compounds that bind to enzymes or receptors can be discovered by finding two fragments that bind and then synthetically combining
첨단화학의 이해Applications of Combinatorial Chemistry
Pharmaceutical industry: rapid synthesis of a huge number of drug-like molecules
Material science: new approach for the discovery of new materials
Catalyst discovery: fast discovery of new catalysts
Chemical biology: diversity-oriented synthesis of small organic molecules
첨단화학의 이해
Supramolecular ChemistrySupramolecular Chemistry
첨단화학의 이해
1. Molecular chemistry- Covalent bond
H2N NH2
O
150 years ago
urea
palytoxin
첨단화학의 이해초분자 화학
2. Supramolecular chemistry- Chemistry beyond moleculesAssembly of molecules – Molecular recognition
1987 노벨화학상 : 초분자화학Charles Pedersen, Jean-Marie Lehn, and Donald J. Cram
Non-covalent bonds: - electrostatic forces- hydrogen bonds- van der Waals interactions- dipole interactions- hydrophobic interactions, etc
첨단화학의 이해DNA and Hydrogen Bonds
N
N
NH2
R
N
NN
N
O
R
H
NH2N
N
N
N
O
O
H
R
NH2
O
R
thymine adenine
guanine cytosine
OBase
O
PO
O
O
첨단화학의 이해DNA and Hydrogen Bonds
NN
N
N
O
RH
NN
N
N
O RH
H
HH
NN
N
N
N
R
NN
N
O
O RH
H
HH
H
Which pair forms stronger hydrogen bonds? And Why?
-
+
+
+
-
-
+
-
+
-
+
-
첨단화학의 이해DNA and Hydrogen Bonds
3.9x108 M-1 3.6x106 M-1 3.3x104 M-1 3.3x104 M-1 3.1x102M-13.6x106 M-1
++++
----
+++-
---+
++-+
--+-
+--+
-++-
+-+-
-+-+
++--
--++
N
NN
H
R
O
H
N
O
H
N
NN
H
R
O
H
N
O
H
2
N
N N
H
R
O
H
N
O
H
첨단화학의 이해New Materials Based on Hydrogen Bonds
N
N N
H
R
O
H
N
O
H
N
NN
H
R
O
H
N
O
H
N
N N
HR
OH
N
O
HN
NN
HR
OH
N
O
H
N
N N
HR
OH
N
O
HN
NN
HR
OH
N
O
H
N
N N
HR
OH
N
O
HN
NN
HR
OH
N
O
H
N
N N
HR
OH
N
O
H
n
첨단화학의 이해Crown Ethers
18-crown-6 15-crown-5
O
O O
O
O O
O
O O
O
O
Na+K+
O
O
O
O
N
O
N
O
O OOOO O
K+K+
Cryptand
- 11 kcal/ mol - 18 kcal/ mol
Crown ether
NO
O
N
ON
CH3
CH3
H3C
N+
H
H H
R
첨단화학의 이해
W.C. Still D.J. Cram
Preorganized Ionophores
O
O
O
OO
O
K+
OO
O
O O
OH H
H HK+
OO
O
OOO
OOMe
O
OOOMe
MeMe MeMe
Preorganization: both binding affinity and selectivity are considerably increased
첨단화학의 이해Anion Recognition
첨단화학의 이해Anion Recognition
첨단화학의 이해Chemosensors
Signals:- fluorescence- color- electric signal...
첨단화학의 이해Chemosensors
ONH
N
CH3H3CN N
OHN
Hg(OAc)2
ONH
NH
CH3H3CN
NH
OS
NH
Hg(ClO4)2, CH3CN(98%)
H2O-MeOH(4 : 1)
1 only Hg2+ Ag+ Cu2+ Cd2+ Pb2+ Zn2+
첨단화학의 이해Carcerand
O
O
+ CO2
첨단화학의 이해
Molecular MachineMolecular Machine
첨단화학의 이해생체 분자기계
ATP Synthase
Bacterial Flagellar Motor
Linear movement - muscle(myosin moving along an actin filament)
첨단화학의 이해Interlocked Molecules
RotaxaneRota (wheel) + axis (axle)
CatenaneCatena (chain)
첨단화학의 이해분자 셔틀 버스 이동
첨단화학의 이해인공 분자기계
A catenane-based switching device for electric circuits.
첨단화학의 이해인공 분자기계
Catenane-based molecular rotor. A unidirectional rotation of the small rings along the large ring is achieved by their sequential complexation and decomplexation with four station parts A-D on exposure to light, heat, and chemical stimuli.
첨단화학의 이해분자 근육
첨단화학의 이해분자 엘리베이터
첨단화학의 이해분자 가위
첨단화학의 이해인공 분자기계
Chiral molecular motor composed of a tetrasubstituted alkene. Photoinduced and thermal-induced unidirectional rotation.
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