Cyclodextrin teknologi - introduktion

6 7

1
Cykliske oligosakkarider

2
 Hydrophobic cavity
Secondary hydroxyl groups

Primary hydroxyl groups

α-CD β-CD γ-CD

13.7 Å 15.3 Å 16.9 Å
5.7 Å 7.8 Å 9.5 Å

7.8 Å

3
Complex formation

guest + host inclusion complex

[GCD]
G + CD GCD Kass = (M-1)
[G][CD]
4
CGTase enzyme

5
Practical production of cyclodextrins

Selective complexants:
α-CD: decanol
β-CD: cyclohexane, limonene, cyclodecanone
γ-CD: cyclohexadec-8-en-1-on, cyclododecaone
Selective precipitation of
one type of cyclodextrin
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Cyclodextrin karakteristika

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Cyclodextrin opløselighed

8
Important cyclodextrin derivatives

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Cyclodextrin struktur

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α-cyclodextrin

β-cyclodextrin

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γ-cyclodextrin

δ-cyclodextrin

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Cyclodextrin kompleksdannelse

Major driving forces for complex formation:

Dipol-dipol interactions
Release of ”high-energy” water
Hydrogen bonds

Hydrophobic interactions van der Waal´s interactions

Solvent effects 13
Cyclodextrins and their typical guests

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Guest-molecules I

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Guest-molecules II

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Guest-molecules III

Misfolded protein

Ad detergent e.g. SDS

Protein-detergent
intermediate

Ad cyclodextrins

+
Active protein !
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Guest-molecules IV

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Guest-molecules V

Anti-aging concentrate:
Vit. C and vit. A-β-CD
complex

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 Possible effects of complex formation between
a guest molecule and α-, β- og γ-cyclodextrin
Enhanced/reduced - aqueous solubility
- bioavailability
Enhanced/reduced stability against - hydrolysis
- oxidation
- UV-light induced degradation
- heat
- reduced volatility
Reduction of unwanted taste and odour

Areas of application:
- Analytical chemistry (e.g. chiral separations)
- Medical industry
- Food industry
- Chemical industry
- Studies of molecular interaction

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Cyclodextrins – for efficient and safe delivery of drugs

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 Selective extraction using cyclodextrins
Removal of cholesterol from eggs and dairy products

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 Cyclodextrins in textile finishing
controlled release of e.g. perfumes

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Analytical chemistry – chiral separations

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Cyclodextrin anvendelse - bioteknologi

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Cyclodextrin anvendelse - bioteknologi

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Enzyme mimics

27
Cyclodextrin-protein interaction Phosphoglycerat kinase

+ 100 mM α-CD buffer

N D
+CD

DCD Dagg

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Cyclodextrin toksikologi

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From Dr. Jens Moldenhauer
Cyclodextrin derivater – ændret selektivitet

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 Large cyclodextrins
Cyclodextrins with DP>8
OH
OH OH
HO O
O O OH
O
HO HO O OH
OH O
O
OH HO
O
HO OH
O

8 O OH
9 HO OH
10, 11, 12…..
6 7 HO
O
OH
O

HO HO O OH
OH
O O
HO
O O O
HO
OH
HO HO

α-CD β-CD γ-CD

13.7 Å 15.3 Å 16.9 Å Analysis ?
5.7 Å 7.8 Å 9.5 Å
Production ?
7.8 Å Structure ?
Properties ?
Complex formation ?
Applications ?
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Large CD producing enzymes

HPAEC-PAD
B. macerans CGTase

Koizumi et al. (1999) J.Chrom.A 852:407

Amylomaltase
D-enzyme
CGTases
6 10 15 20 25 30 35
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D.P.
Purification of large CD
High D.P.
CD9 ? ALL ! mixtures

Selective precipitation Chromatography

Amylomaltase
D-enzyme
CGTases
6 10 15 20 25 30 35
D.P.
Chemical synthesis CD9
Wakao et al. (2002) J.ORG.CHEM. 67:8182
3 x maltotriose 33
Store cyclodextriner - oprensning

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Store cyclodextriner - karakteristika
Table 1: Nomenclature and some properties of cyclodextrins.
Glycosyl Semisystematic name Generic namea Abbreviation Molecular Aqueousd,e Surface tentiond,e Specifice Half life ofe,f
units weight solubility (mN/m) rotation [α]25 D ring opening
[g per 100 ml] (h)
6 cyclomaltohexaose α-cyclodextrin α-CD 972.9 b 14.5 72 147.8 33
7 cyclomaltoheptaose β-cyclodextrin β-CD 1135.0b 1.85 73 161.1 29
8 cyclomaltooctaose γ-cyclodextrin γ-CD 1297.2b 23.2 73 175.9 15
9 cyclomaltononaose δ-cyclodextrin CD 9 1459.3b 8.19 73 187.5 4.2
10 cyclomaltodecaose ε-cyclodextrin CD 10 1621.4b 2.82 72 204.9 3.2
11 cyclomaltoundecaose ζ-cyclodextrin CD 11 1783.6b >150 72 200.8 3.4
12 cyclomaltododecaose η-cyclodextrin CD 12 1945.7b >150 72 197.3 3.7
13 cyclomaltotridecaose θ-cyclodextrin CD 13 2107.9b >150 72 198.1 3.7
14 cyclomaltotetradecaose ι-cyclodextrin CD 14 2270.0b 2.30 73 199.7±1.0 3.6
15 cyclomaltopentadecaose κ-cyclodextrin CD 15 2432.2b >120 73 203.9±0.4 2.9
16 cyclomaltohexadecaose λ-cyclodextrin CD 16 2594.3b >120 73 204.2±0.7 2.5
17 cyclomaltoheptadecaose µ-cyclodextrin CD 17 2756.4b >120 72 201.0±0.6 2.5
18 cyclomaltooctadecaose ν-cyclodextrin CD 18 2918.6b - - - -
19 cyclomaltononadecaose ξ-cyclodextrin CD 19 3080.7b - - - -
20 cyclomaltoeicosaose ο-cyclodextrin CD 20 3242.9b - - - -
21 cyclomaltoheneicosaose π-cyclodextrin CD 21 3405.0b - - - -
22 cyclomaltodoicosaose - CD 22 3567.2c - - - -
23 cyclomaltotriicosaose - CD 23 3729.3c - - - -
24 cyclomaltotetraicosaose - CD 24 3891.4c - - - -
25 cyclomaltopentaicosaose - CD 25 4053.6c - - - -
26 cyclomaltohexaicosaose - CD 26 4215.7c - - - -
27 cyclomaltoheptaicosaose - CD 27 4377.9c - - - -
28 cyclomaltooctaicosaose - CD 28 4540.0c - - - -
29 cyclomaltononaicosaose - CD 29 4702.2c - - - -
30 cyclomaltotriacontaose - CD 30 4864.3c - - - -
31 cyclomaltohentriacontaose - CD 31 5026.5c - - - -
n - - CD n n·162.14 - - - -
a
[22-27], b calculated from the molecular formula and confirmed by mass spectroscopy [22-28], c
calculated from the molecular formula and confirmed by mass spectroscopy [28], d observed at
25°C, e [24, 51], f In 1M HCl at 50 °C.
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δ-cyclodextrin egenskaber

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Store cyclodextriner – kompleks dannelse

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Fujiwara et al. (1990) Chem.Lett. 739 Saenger et al. (1998) Chem.Rev. 98:1787 Harata et al. (1998) Supramol.Chem. 9:143
Endo et al. (1999) Anal.Sci. 15:613 Saenger et al. (1998) Chem.Rev. 98:1787

CD9 CD10 CD14

2x

CD26 CD21 CD26

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Saenger et al. (1998) Chem.Rev. 98:1787 Kitamura (2000) Cyclic Polymers 125
CD26-krystalstruktur
CD26- krystalstruktur
V-amylose

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”Cycloamylose” - properties

Property ”Cycloamylose” Amylose

Degradation Fast Fast
(α-amylases)
Solubility High Low
Viscosity Low High
Retrogradation - +
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