Online Thesis Search Results

TITLE
CERTIFICATE
DECLARATION
ACKNOWLEDGEMENT
DEDICATION
CONTENTS
ABBREVIATIONS
1 Introduction and Objectives
1.1 Introduction
1.2 Objectives of the Work
1.3 Organization of the Thesis
2 Solid Phase Peptide Synthesis - Impact and Concepts: A Retrospect
2.1 Introduction
2.2 The Solid Phase Principle
2.3 Strategies in SPPS
2.4 Solid Supports
2.4.1 Gel Supports
2.4.2 Composite Support.
2.4.3 BrP.h Polymers and Surface Type Supports
2.5 Protection Chemistry
2.6 Foci versus Boc Chemistry
2.7 Peptide Bond Formation
2.8 Handles, Linkers and Spacers for Solid Phase Peptide Synthesis
2.9 Problems in Peptide Synthesis
2.9.1 Polymer Matrix Effect
2.9.2 Difficult peptides
2.9.3 Side Reactions
2.10 Peptide and Protein Synthesis by SPPS
2.11 Purification and Characterisation of Peptides
2.12 Conclusion and Outlook
3 Preparation, and Optimization of 1, 4-Butanediol Dimethacrylate Cross linked Polystyrene Support
3.1 Introduction
3.2 Preparation of 1, 4-Butanediol Dimethacrylate and Divinylbenzene Cross linked Polystyrene Supports
3.3 Characterisation of the BDDMA-PS
3.4 Swelling Studies
3.5 Fictionalization of Support
3.5.1 Chloromethylation of 2-100/0 BDDMA-PS (la-69) and 2%DVB-PS (7a)
3.5.2 Hydmxgmethyl BDDMA-PS Resin (2d)
3.5.3 Hydroxymethylphenethyl BDDMA-PS (EMP-BDDMA-PS)
3.6 Resin Stability
3.7 Reactivity Studies
4 Peptide Synthesis
Part A: Synthesis of Model Peptides and Difficult Sequence Peptides
4.1 Synthesis of Model Peptides
4.1.1 Synthesis of the Peptide la, LGG
4.1.2 Synthesis of the peptide 2a, GLG
4.1.3 Synthesis of the Peptide 3a, and 4a (PGPG and FGK)
4.1.4 Synthesis of the Peptide lb, IACW
4.1.5 Synthesis of (Ala) 3-Val (2b)
4.1.6 Synthesis of VELG and LAVa (3b and 4b)
4.2 Synthesis of Difficult Sequence Peptides
4.2.1 A Comparative Study on the Synthesis of Peptide LMVGGVVIA (B 34-42) using 2% BDDMA-PS and Merrifield Resin
4.2.2 Synthesis of Peptides VAVAG and VIVIG
4.2.3 Synthesis of the Peptides VQAAIDYING and QVGQVELG Part B: Synthesis of Diazepam Binding Inhibitor Fragments
Part B: Synthesis of Diazepam Binding InhibitorFragments
4.3 Introduction
4.3.1 Synthesis of the Peptide FTGK (DBI 67-70)
4.3.2 Synthesis of the Peptide IYGHYK (1313145-40)
4.3.3 Synthesis of the Peptide KQATVGD (DBI 51-56)
4.3.4 Synthesis of the Peptide GLLDLK (rDBI 45-50)
4.3.5 Synthesis of the Peptide RPGMLDFTGK (DBI 61-70)
4.3.6 Synthesis of the Peptide QATVGDINTERPGMLDFTGK (DBI 51-70)
4.3.7 Synthesis of the Peptides PSDEEMLFIYGHYK (DBI 37-50) and LKTKPSDEEMLFIYGHYK (DBI 33-50)
5 Experimental
5.1 Materials and Methods
5.2 Purification of Solvents
5.3 Preparation of BDDMA-Cross linked Polystyrene
5.4 Preparation of 2% DVB-Cross linked Polystyrene
5.5 Functionalisation of Cross linked Polymers (BDDMA-PS and DVB-PS)
5.5.1 Preparation ofChloromethy1 Methyl ~ther
5.5.2 Preparation of 1 M ZnCla in THF~
5.5.3 Chloromethylation of the BDDMA and DVB-CrosslinkedStyrene Copolymers (2a-7a)
5.5.4 Estimation of Chlorine Capacity: Pyridine -on ~ e t h o d ~
5.5.6 Reparation of Hydroxpmethyl BDDMA-PS (2d)
5.5.7 Reparation of 4-hydroxymethylphenorpmethyl BDDltdA-P8 (EMP-BDDW-FS) 5m (28)
8.5.8 Determination of Hydroxyl Group Capacity
5.6 Swelling Studies
5.7 Preparation of Boc Azide
5.8 Preparation of Boc Amino Acids (Schnabels method)
5.9 General Methods Adopted for SPPS
5.9.1 Attachment of first Amino acid
5.9.2 &timation of Degree of Amino add incorporation
5.9.3 R Ikprotection Procedures
5.9.4 Coupling Procedures
5.9.5 Cleavage of the Peptide fram the Support
5.9.6 Ruification of the Crude Peptides
5.9.7 Characterisation of the Peptides
5.9.8 Monitoring of the Capling Reactiop) %Jwr T&
5.10 Attachment of Boc-Lys (2C1-Z) to the Chloromethylated Resins
5.11 Reactivity Study-Acylation of Lysine Residue Attached to Polymers 2a-7a by Boc-Aia-OBt
5.12 Solid Phase Synthesis of Peptides
5.12.1 Synthesis of Model Peptides
a. Attachment of C-termlnrl Amiuo adds
b. Synthesis of LGG (la)
c. Synthesis of GLG (Za)
d. Synthesis of PGPG
e. Synthesis of PGK
f. Cleavage of the Peptides 18-49 from the Support
g. Synthed. of the Peptide IALWF (lb)
h. Synthesis of the peptide AMV (2b)
i. Synthesis of the Pep; ida VECC (3b) and LAW3 (4b)
j. Cleronge of the Peptides lb-4b from the Support
k. Characterisation of the peptides 1b-4b
5.12.2 Synthesis of Difficult Sequence Peptides
a. Attachment of GtermfPP1 Amino adds
b. Synthesis of the Peptide 5% LHVGGVVU (p - 34-42) onBDDMA-PS (20) and Merrifield Resin (70)
c. Synthesis of the peptide 6a and 7a (VAVAG sad WVIQ)
d. Synthesis of the Peptide VQAAIDYING (5b)
e. Synthesis of the Peptide QVGQVELG (6b)
5.12.3 Synthesis of DBI Fragments
a. Attachment of C-terminal Amino adds
b. Synthesis of the Peptide 89-1 la
c. Synthesis of tha Peptide 7b
d. Synthesis of the Peptide 8b-lob
Summary and Outlook
References
CURRlCULUM VITAE