Online Thesis Search Results

TITLE
CERTIFICATE
DECLARATION
ACKNOWLEDGEMENT
DEDICATION
CONTENTS
ABBREVIATIONS
I. INTRODUCTION AND OBJECTIVES
Objectives of the Present Work
Organization of the Thesis
II. ROLE OF THE POLYMER SUPPORT IN THE SOLID PHASE SYNTHESIS OF PEPTIDES
1. Influence of the degree of cross linking and topographical nature of the polymer matrix
2. Polyacrylamide-type support
3. Polystyrene-polyethylene glycol graft polymers as supports
4. Salvation and swelling of peptide resins
5. Design of new supports with superior swelling properties
III. EXPERIMENTAL
Materials and Methods
1. Source of chemicals
2. Physical measurements
3. Preparation of reagents
a) 4N HCL-dioxane
b) Chloromethylmethylether
c) Boc Azide
d) Preparation of Palladium Black
4. Preparation of amino acid methyl / ethyl esters
5. Synthesis of Boc-amino acids
a) Schnabel Method
b) 2- (t-butoxycarbonyloxyimino) -2-phenylacetonitrile (Boc-ON) method
c) Preparation of Boc-Arg (Mts) -OH
i) preparation of N-Carbobenzyloxy L-Arg
ii) Preparation of 2-Arg (Mts) -OH
iii) Removal of Benzyloxycarbonyl (Z) group: Preparation of Boc-Arg (Mts) -OH
6. Analysis of protected amino acids
7. Estimation of halogen content in functionalized tetraethyleneglycol diacrylate (TTEGDA) -cross linked polystyrene resins
8. Attachment of first amino acid to the resin
9. Estimation of amino group by picric acid method
10. General procedure for solid phase synthesis of peptides
11. General procedure for photolytic cleavage
12. Column chromatography
13. Thin layer chromatography
i) Ninhydrin
ii) Chlorine-Starch-Potassium Iodide Reagent (Rydons Reagent)
iii) Iodine
iv) Sakaguchi Reagent
14. Amino acid analysis
15. Preparation of Polymeric supports
i) Solution copolynerisation of styrene and tetraethyleneglycol diacrylate
ii) Preparation of tetraethyleneglycol diacrylate crosslinked polystyrene supports suspension polynerisation
16. Functionalization of Tetraethyleneglycol Diacrylate-Crosslinked polystyrene support
i) Chloromethylation of tetraethyleneglycol diacrylate-crosslinked polystyrene support
ii) Preparation -of aminomethyl tetraethyleneglycol diacrylate-crosslinked polystyrene resin
iii) Preparation -of 4-chloromethyl-3-nitrotetraethyleneglycol diacrylate polystyrene
iv) Preparation -of α -bromopropionyl tetraethylene glycol diacrylate-crosslinked polystyrene resin
v) Preparation of α- minopropionyl resin& -aminopropionyl resin
vi) Preparation -of 4-bromonethyl benzoic acid
vii) Preparation -of 4-bromomethyl-3-nitrobenzoic acid
viii) Preparation -of 4-bromonethyl-3-nitrobenzanidomethyl tetraethyleneglycol diacrylate crosslinked polystyrene resin
ix) Preparation of 4-aminomethyl-3-nitrobenzamidomethyl tetraethyleneglycol diacrylate polystyrene resin
X) Preparation -of 4-hydroxynethyl phenoxymethyl tetraethyleneglycol diacrylate-crosslinked polystyrene resin (l0)
17. Solvent imbibition measurements of TTEGDA-cross linked polystyrene resin
18. Stability studies of TTEGDA crosslinked polystyrene resin
19. Synthesis of protected peptides using 4-chloromethyl-3-nitro TTEGDA cross linked polystyrene support
i Synthesis -of Boc-Met-Leu-Ala-OMe
ii) Prepara-ion of Boc-Ala-Val-Gly-OEt
iii) Preparation -of Boc-Met-Leu-Phe-OMe
iv) Synthesis -of Boc-Val-Gly-OEt
v) Synthesis of Boc-Val-Gly-OEt -DCC coupling of Boc-Val and Gly-OEt
vi) Preparation of Boc-Phe-Gly-OEt
20. Synthesis of Boc (Ala-Leu-Ala) 4OMe peptide on high-capacity chloromethyl TTEGDA-cross linked polystyrene resin
i) Cleavage of Boc (Ala-Leu-Ala) OMe from the Solid Support by Trans-esterification
21. Synthesis of model peptides on 4-bromomethyl-3-nitrobenzamidomethyl TTEGDA-cross linked polystyrene support
i) Esterification of Boc-Leu with Bromomethyl resin
ii) Solid Phase synthesis of Boc-Leu-Leu-Leu-Leu
iii) Solid Phase Synthesis of Boc-Gly-Val-Ala-Leu
22. Synthesis of Boc-Val-Glu (OBzl) -Ala Leu-Tyr (Bzl) -Leu-NH2 on 4-amino methyl-3-nitrobenzamidomethyl TTEGDA cross linked polystyrene resin
23. Solid phase synthesis of Boc-Met Phe-Leu-OH using A-bromopropionyl TTEGDA-cross linked polystyrene support
24. Synthesis of Boc-Leu-Ala-Gly-Val-NH2 and Boc-Phe-Phe-Gly-Leu-NH2 using α -aminopropionyl TTEGDA-cross linked polystyrene resin
1) BOC-Phe-Phe-Gly-Leu-Met-NH2
25. Synthesis of biologically important peptides using chloromethyl TTEGDA crosslinked polystyrene resin
i) Synthesis of Deltorphin: Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2
ii) Synthesis of cytoadhesive inhibitory peptide: Gly-Arq-Gly-Asp-Ser-Pro
iii) Cleavage of Gly-Arg-Gly-Asp-Ser-Pro from the peptide resin (22) using trifluoroacetic acid
iv) Synthesis -of Gly-Arg-Gly-Glu-Ser-Pro
v) Synthesis of nuclear signal sequence Ser-Thr-Pro-Pro-Lys-Lys-Lys-Arg-Lys-Val-Cys (Acm)
26. Synthesis of pardaxin sequences 16-33, 5-33 and 1-33
i Cleavage of 16-33 pardaxin pepkide from the resin- (22) using trifluoroacetic acid
ii) Cleavage of the 5-33 pardaxin from the resin (23) using trifluoroacetic acid
iii) Cleavage of the 33-residue pardaxin peptide-toxin from the resin (24) usinq trifluoroacetic acid
27. Manual microsequencing of (5-33) and (1-33) pardaxin
1. Set-up
2. Coupling
3. Washing
4. Extraction
5. Conversion
28. Synthesis of pardaxin (1-26) hydrophobic segment on high capacity chloromethyl TTEGDA crosslinked polystyrene resin
i) Cleavage of 1-26 pardaxin segment from the resin (25) using trifluoroacetic acid
ii) Purification of 1-26 pardaxin peptide
iii) Automatic Edman degradation of 1-26 seqment of pardaxin sequence
IV. TETRAEHYLENEGLYCOL DIACRYLATE (TTEGDA) CROSSLINKED POLYSTYRENE: A NEW POLYMERIC SUPPORT FOR PEPTIDE SYNTHESIS
Results and Discussion
1. Polymer synthesis
2. Functionalization of tetra ethylene glycol diacrylate (TTEGDA) -cross linked polystyrene resin
Fig.IV.1 Scanning Electron Micrograph of TTEGDA Crosslinked Polystyrene Beads
3. Preparation of chloromethyl resin
4. Preparation of 4-chloromethyl-3 nitro TTEGDA-cross linked polystyrene resin
5. Introduction of amino methyl groups in TTEGDA-cross linked polystyrene resin
6. Preparation of α-bromopropionyl and α-aminopropionyl TTEGDA-cross linked polystyrene resin
7. Preparation of 4-bromomethyl-3nitrobenzamidomethyl and 4-aminomethyl-3-nitrobenzamidomethyl TTEGDA-cross linked polystyrene
8. Preparation of 4- (hydroxymethyl) phenoxymethyl TTEGDA-cross linked polystyrene
9. Characterization of TTEGDA-cross linked polystyrene
10. Swelling, salvation and stability of TTEGDA-cross linked polystyrene
V. PEPTIDE SYNTHESIS USING TETRAETHYLENEGLYCOL DIACRYLATE (TTEGDA) -CROSS LINKED POLYSTYRENE SUPPORTS
Results and Discussion
1. Synthesis of protected model peptides on 4-chloromethyl-3-nitro TTEGDA-cross linked polystyrene
2. Mechanism of photolysis
3. Synthesis of Boc (Ala-Leu-Ala) 4-OMe on a high capacity chloromethyl TTEGDA-cross linked polystyrene
Fig.v.1.a) Scanning Electron Micrographs of TTEGDA crosslinked polymer Beads
Fig.v.1.b) A Single Bead Enlarged from Fig.v.1.a
4. Synthesis of protected peptide segments on photosensitive 4-bromomethyl-3-nitrobenzamidomethyl TTEGDA-cross linked polystyrene
i) Synthesis of Boc -Leu-Leu-Leu-Leu
ii) Synthesis of Boc-Gly-Val-Ala-Leu
5. Synthesis of peptide amides on 4-aminomethyl-3-nitrobenzamidomethyI TTEGDA-cross linked polystyrene
6. Synthesis of Boc-Met-Phe-Leu using α-bromopropionyl TTEGDA-cross linked polystyrene
7. Synthesis of peptide amides using α-aminopropionyl TTEGDA-cross linked polystyrene
8. Synthesis of substance P (7-11) segment on α -aminopropionyl TTEGDA crosslinked polystyrene
9. Synthesis of opioid agonist deltorphin on high capacity chloromethyl TTEGDA-cross linked polystyrene
10. Synthesis of cytoadhesive inhibitory peptides Gly-Arg-Gly-Asp / Glu-Ser-Pro on high capacity chloromethyl TTEGDA-cross linked polystyrene
11. Synthesis of nuclear signal sequence on chloromethyl TTEGDA crosslinked polystyrene
12. Synthesis of pardaxin, a 33-residue peptide toxin, on high capacity TTEGDA-cross linked polystyrene
13. Synthesis of pardaxin sequence (16-33), (5-33) and (1-33)
14. Synthesis of 26-residue peptide corresponding to the N-terminal hydrophobic region of pardaxin on high capacity TTEGDA-cross linked polystyrene
VI. SUMMARY AND OUTLOOK
VII REFERENCES