Online Thesis Search Results

TITLE
DEDICATION
CERTIFICATE
DECLARATION
ACKNOWLEDGEMENT
CONTENTS
ABBREVIATIONS
1. INTRODUCTION AND OBJECTIVES
References
2. SOLID PHASE PEPTIDE SYNTHESIS-A REVIEW ON RECENT DEVELOPMENTS
2.1. Principles of Merrifields Peptide Synthesis
2.2. The Role of Solid Support
2.3. New Approaches in Solid Phase Peptide Synthesis
2.3.a. Resin peptide linkages
2.3.b. Multi-detachable handle supports in SPPS
2.3.c. Photolysis-an efficient method for the synthesis of protected peptides in SPPS
2.3.d. Linkers for miscellaneous protection of peptides
2.3.e. Use of Fmoc- amino acids-a mild procedure for SPPS
2.3.f Polymeric carboxyl protection
2.3.g. Sequential attachment of amino acids and deprotection
2.3.h. Detachment of peptide from the support
References
3. SYNTHESIS, FUNCTIONALISATION AND CHARACTERIZATION OF 1, 4-BUTANEDIOL DIMETHACRYLATE CROSS-LINKED POLYSTYRENE (PS-BDODMA)
3.1. Introduction
3.2. Results and Discussion
3.2.a. Synthesis of BDODMA- cross linked polystyrene (PS-BDODMA) support
3.2.b. Characterization of PS-BDODMMA support
3.2.c. Swelling and stability studies of polymer support
3.2.d Functionalisation of PS-BDODMA resin
1. Chloromethylation
2. Hydroxymethylation
3. Aminomethylation
3.2.e. C-terminal amino acid incorporation to PS-BDODMA resin
3.2.f. Time-dependent cleavage of Boc-amino protection
3.2.g. Time-dependent cleavage of Fmoc-amino protection
3.2.h. Temperature-dependence in the rate of amino acid coupling in SPPS
3.2.i. Time and temperature-dependent cleavage ofpeptides
3.3. Experimental
3.3.a. Materials and methods
3.3.b. Preparation of chloromethyl methyl ether
3.3.c. Preparation of PS-BDODMA support by suspension polymerization
3.3.d. Swelling studies
3.3.e. Stability studies
3.3.f. Functionalisation of PS-BDODMA resin
1. Chloromethylation
2. Hydroxymethylation
3. Aminomethylation
3.3.g. Preparation of PS BDODMA-HMPA resin
3.3.h. Preparation of PS-DVB-HMPA resin
3.3.i. Esterification of Boc-amino acid to chloromethyl resin
3.3.j. Time-dependent esterification of Boc-amino acids to PS-BDODMA and PS-DVB resins
3.3.k. Esterification of Fmoc-amino acid to polymer support using MSNT
3.3.l. Time-dependent esterification of Fmoc-amino acid to PS-BDODMA, PS-BDODMA-HMPA, PS-D VB and PS-DVB-HMPA resins
3.3.m. Time-dependent Boc-deprotection
3.3.n. Time-dependent Fmoc-deprotection
3.3.o. Time-dependent coupling of amino acids at different temperatures
3.3.p. Detachment of peptide from PS-BDODMA support
References
4. PS-BDODMA RESIN, MERRIFIELD RESIN AND SHEPPARD RESIN IN PEPTIDE SYNTHESIS- A COMPARATIVE STUDY
4.1. Introduction
4.2. Results and Discussion
4.2.a. 4-Hydroxymethyl phenoxyacetamidomethyl 2% butanediol dimethacrylate cross-linked polystyrene (PS-BDODMA-HMPA) resin
4.2.b. p-[ (R, S) -a- (I- (9H-fluoren-9- yl) methoxyformamidol-2, 4 dimethoxybenzyl]-phenoxyacetamidomethyl 2% butanediol dimethacrylate cross-linked polystyrene (PS-BDODMA-Rink amide) resin
4.2.c. Synthesis and characterization of peptides
1. Synthesis of Leu-Gly-Ala-Val
2. Synthesis of (65- 74) fragment of Acyl carrier protein
3. Synthesis of Leu-Gly-Ala-Leu-Gly Ala
4. Synthesis of Ala-Ala Ala Ala
5. Synthesis of 25-residue fragment of NS I region of Hepatitis C viral
6 Synthesis of 14-residue and I0-residue fragments of NS 1 region of Hepatitis C viral polyprotein
4.3. Experimental
4.3.a. Materials
4.3.b. Preparation of Boc-azide
4.3.c. Preparation ofanzino acid derivatives
1. Amino acid methyl / ethyl esters
2 Boc-amino acids (Schnabels method)
4.3.d. Preparation of 1-Hydroxybenzotriazole (HOBt)
4.3.e. Methods. fur the purification and detection of peptides
4.3.f. Preparation of PS-BDODMA-HMPA resin
4.3.g. Preparation of PS-D VB-HMPA resin
4.3.h. Preparation of Sheppard-HMPA resin
4.3.i. Preparation of Fmoc-Val-D-CH2-C6H4-O-CH2-CO-NHC6H4-PS- BDODMA resin
4.3.j. Preparation of Fmoc-Val-O-CH2-CJ-I4-O-CH2-CO NH-C6H4-PS-DVB resin.
4.3.k. Preparation of Fmoc-Val-O-CHZ-C6H4-O-CH2-CO-NH-C6H4-Sheppard resin
4.3.l. Preparation o f Fmoc-Gly-O-CH2-C6H4-O-CH2-CO-NH-C6H4-PS BDODMA resin
4.3.m. Preparation of Fi7zoc-Gly-O-CHr-C6FI4-O-CHrCO-NH-C6H4-PS-DVB resin.
4.3.n. Preparation of Fmoc-G4-O-CH2-C6H4 O-CHrCO-NH-C6H4 Sheppard resin
4.3.o. Preparation of PS-BDODMA-Rink amide resin
4.3.p. Preparation of PS-DVB-Rink amide resin
4.3.q. Preparation of Fmoc-Ala-NH- (H3CO) 2C6H3-CH-C6H4-O-CH2-CO-NH-CH2-C6H4-PS-BDODMA resin
4.3.r. Preparation of Fmoc-Ala-NH- (H3CO) 2C6H3-CH-C6H4-O-CH2-CO NH-CH, -C6H4-PS DVB resin
4.3.s. Peptide Synthesis
1. Synthesis of Leu Ala-Gly-Val
2 Synthesis of Val-Gln-Ala-Ala-Ile-Asp-Tyr-Ile Asn-Gly (acyl carrier protein fragment)
3. Synthesis of Leu-Gly- Ala-Leu-Gly- Ala
4. Synthesis of Ala-Ala-Ala-Ala
5. Synthesis o f Leu-Ile-Asn-Thr-Asn-Ala-Ser-Trp-His-Ala-Asn-Arg-Thr-Ala-Leu-Ser-Asn-A.sp-Ser-Lys-Leu-Asn-Thr-Gly- Ala-NH2
6. Synthesis of Leu-Ile-Asn-Thr-Asn-Ala-Ser-Trp-His- Ala-Asn-Arg Thr-Ala-NH2
7.Synthesis of Leu- Asn-Cys (Acm) Asn- Asp-Ser-Leu- Asn-Thr-Ala- NH2
References
5. SYNTHESIS OF BIOLOGICALLY ACTIVE PEPTIDES ON PS-BDODMA RESIN USING BOC-CHEMISTRY
5.1. Introduction
5.2. Results and discussion
5.2.a. Synthesis of model peptides on PS-BDODMA resin using Boc-chemistry
1. Synthesis of Phe-Phe-Thr-Lys-Phe-Lys-Ser-Gln
2. Synthesis of Val-Gln-Gln-Gly-Pro-Trp-Gly-GlyAla-Ala-Val
3. Synthesis of Val-Asn-Asn-Gln-Gln-Asn-Asn-Ile-Gly-Gln-Gln-Gly Ala-Ala-Vol
4. Synthesis of (Val) 10
5. Synthesis of Val-Gln-Asn-Asn-Val-Val-Val-Val-Val
6. Synthesis of Pro- Vat- Val-Thr-Thr- Vat- Val- Vat- Val-Asn
7. Synthesis of Thr- Val- Val- Val- Val- Asn
8. Synthesis of Pro-Met-Leu-Phe-Val-Thr
9. Synthesis of Val Met-Leu-Phe-Leu-Pro
10. Synthesis of Met-Leu-Phe-Tyr-Val-Gly
5.2.b. Synthesis of protected peptides
1. Synthesis of Boc-Met-Leu-Phe-Cys (Acm) -Lys (Cl-Z) -Vat-OMe
2. Synthesis of Boc-Pro- Met-Leu-Phe-Val-Thr-OMe
3. Synthesis of Boc-Val- Met-Leu-Phe Leu-Pro-OMe
4. Synthesis of Boc Met-Leu-Phe-Tyr (Bzl) -Teal-Gly-OMe
5.2.c. Synthesis of biologically active peptides
1. Synthesis of Leucine enkephalin (Tyr-Gly-Gly-Phe-Leu)
2. Synthesis of 3-casomorphin (Bovine) (Tyr-Pro-Phe-Pro-Gly-Pro- Ile)
3. Synthesis o f 3-casomorphin (Human) (Tyr-Pro-Phe-Val-Glu-Pro-Ile)
4. Synthesis of C-reactive protein (77-82) (Val-Gly-Gly-Ser-Glu-Ile)
5. Synthesis of 33-42 fragment of Alzheimers 3-amyloid peptide (Gly-Leu-Met-Val-Gly-Gly-Val-Val-lle-Ala)
6. Synthesis of inhibitor of Ribonucleotide Reductase of Herps Simplex Virus-Type I (Tyr- Ala-GlyAla-Val-Val-Asn-Asp-Leu)
7. Synthesis of Scyliorhinin I peptide (Ala-Lys-Phe Asp-Lys-Phe-Tyr Gly-Leu-Met)
8. Synthesis of 43-residue peptide from a CD 4 binding domain of Human Immunodeficiency Virus Envelope Glycoprotein
5 3. Experimental
5.3.a. General procedure for solid phase peptide synthesis
1. Phe-Phe-Thr-Lys-PheLys-Ser-Gln
2. Val-Gin- (rIn-Gly-Pro-Trp-Gly-GlyAla-Ala-Val
3. Val-Asn--Asn-Gln-Gln-Asn-Asn-Ile-Gly-Gln-Gln-Gly- Ala- Ala-Val
4 (VaI) 10
5. Val-GIn-Asn-Asn-Val-Val-Val-Val-Val
6. Pro- Vcrl-Val-Thr-Thr-Val-Val-Val-Val-Asn
7. Thr-Vol-Val-Vol- Val-Asn
8. Pro-Met-Leu-Phe-Val-Thr
9. Val-Met-Leu-Phe-Leu-Pro
10. Met-Leu-Phe-Tyr-Val-Gly
11. Boc-Met-Leu-Phe-Cys (Acm) -Lys (Cl-Z) -Val-OMe
12. Boc-Pro-Met-Leu-Phe-Val-Thr-OMe
13. Boc-Val-Met -Leu-Phe-Leu-Pro-OMe
14. Boc-Met-Leu-phe-Tyr (Bzl) -Yal-Gly-OMe
15. Synthesis of Leucine enkephalin (Tyr-Gly-Gly-Phe-Leu)
16. Synthesis of b-casomorphin (Bovine) (Tyr-Pro-Phe-Pro-Gly-Pro-Ile)
17. Synthesis of b-casomorphin (Human) (Tyr-Pro-Phe-Val-Glu-Pro- Ile)
18. Synthesis of C-reactive protein (77-82) (Val-Gly-Gly-Ser-Glu-Ile)
19. Synthesis of 33-42 fragment of Alzheimers b-amyloid peptide (Gly-Leu-Met-Val-Gly-Gly-Yal-Val-lle- Ala)
20. Synthesis of inhibitor of Ribonucleotide reductase of Herps Simplex Virus-type 1 (Tyr- Ala-Gly-Ala-Val-Val-Asn-Asp-Leu)
21. Synthesis of Scyliorhinin I peptide (Ala-Lys-Phe-Asp-Lys-Phe Tyr-Gly-Leu-Met)
22. Synthesis of 43-residue peptide from a CD 4 binding domain of Human Immunodeficiency Virus Envelope Glycoprotein
References
6. SYNTHESIS OF BIOLOGICALLY ACTIVE PEPTIDES ON PS-BDODMA SUPPORT USING FMOC-AMINO ACIDS
6.1. Introduction
6.2. Results and Discussion
6.2.a. Synthesis of 4- (4-hydroxymethyl-3-methoxyphenoxy) butylamidomethyl 2% PS-BDODMA (PS-BDODMA-HMPB) resin
6.2.b Synthesis of peptides
1. Synthesis of 1-15 fragment of Esculentin-1 (Gly-Ile-Phe-Ser-Lys Leu-Gly-Arg-Lys-Lys-Ale-Lys-Asn-Leu-Leu)
2. Synthesis ref 1-15 fragment of Esculentin-1 modified at Gly7 by Pro Gly-Ale-Phe-Ser-Lys-Leu-Pro-Arg-Lys-Lys-Ile-Lys- Asn-Leu-Leu)
3. Synthesis of 33-44 fragment of Esculentin-1 (Thr-Gly-Ale-Asp-Ile-Ala-GI v- (.ys (Acm) -Lys-Ale-Lys-Gly)
4. Synthesis of 33-44 fragment of Esculentin-Imodified at Gly39 by Ala (Thr-Gly-lle-Asp-Ile-Ala- Ala-Cys (Acm) -Lys-Ale-Lys-Gly)
5. Synthesis of 9-27 fragment of Esculentin-1 (Lys Asn-Val-Gly-Lys-Ghr-Val-Gly-Met-Asp-Val-Val- Arg-Thr-Gly-Ale-Asp-Ale-Ala)
6. Synthesis of 9-27 fragment of Esculentin-1 modified by replacing Glu and Asp by Lys (Lys-Asn-Val-Gly-Lys-Lys-Val-Gly- lle-Lys-Val-Val-Arg-Thr-Gly-Ale-Lys-Ale-Ala) Synthesis of 9-27 fragment of Esculentin-1 modified by replacing Gly with Ala and Asp & Glu with Lys (Lys-Asn-Val- Ala-Lys Lys-Val Ala-Met-Lys- Val- Val-Arg-Thr-Gly-Ile-Lys-lle-Ala)
7. Synthesis of 9-27 fragment of Esculestin-1 modified by replacing Gly with Alaand Asp & Glu with Lys
6.3 Experimental
6.3.a. Preparation of reagents and amino acid derivatives
6.3.a.1. Synthesis of Fmoc-amino acids using fluorenyl methyl -chloroformate
6.3.a.2. Synthesis of Fmoc-amino acids using fluorenyl methyl succinimidyl carbonate
6.3.a.3. Preparation of 4- (4-hydroxymethyl-3-methoxyphenoxy) butylamidomethyl 2% PS-BDODMA (PS-BDODMA-HMPB) resin
6.3.a.4. Preparation of Fmoc Ala-O-CH2-C6H3 (O (CH3) -O-CH2-NHCO-CH2-C6H4-resin
6.3.a.5. Preparation of Fmoc-Leu-O-CH2-C6H4-resin
6.3.a.6. Preparation of Fmoc-Gly-O-CH2-C6H4-resin
6.3.a.7. Synthesis of peptides
1. Synthesis of 1-15 fragment of Esculentin-1 (Glv-Ile-Phe-Ser-Lys-Leu-Gly-Arg-Lys-Lys-Ile-Lys- Asn-Leu-Leu)
2. Synthesis of 1-15 fragment of Esculentin-1 modified at Gly7 by Proline (Gly-lle Phe-Ser-Lys-Leu-Pro-Arg-Lys-Lys-Ile-Lys-Asn-Leu-Leu)
3. Synthesis of 33-44 fragment of Esculentin-1 (Thr-Gly Ile-Asp- Ile-Ala-Gly-Cys (Acm) -Lys-Ile-Lys-Gly)
4. Synthesis of 33-44 fragment of Esculentin-I modified at Gly39 by Ala (Thr-Gly-Ile-Asp-Ile Ala-Ala-Cys (Acm) Lys-Ile-Lys-Gly)
5. Synthesis of 9-27 fragment of Esculentin-1 (Lys Asn-Val-Gly-Lys-Glu-Val-Gly-Met- Asp-Val-Val-Arg-Thr Giy-Ile-Asp-Ile Ala)
6. Synthesis of 9-27 fragment of Esculentin-1 modified by replacing Glu and Asp by Lys (Lys-Asn-Val-Gly-Lys-Lys Val-Gly-Met-Lys-Val-Vat Arg-Thr-Gly-lle-Lys-Ile-Ala)
7. Synthesis of 9-27 fragment of Esculentin-1 modified by replacing Gly with Ala and Glu & Asp by Lys (Lys -Asn-Vat Ala Lys Lys-Val Ala Met Lys-Val-Val- Arg-Thr-Gly-Ile-Lys-Ile -Ala)
References
7. SYNTHESIS OF PROTECTED PEPTIDE ACIDS, AMIDES AND ALKYL AMIDES USING PHOTOLYTICALLY CLEAVABLE PS-BDODMA SUPPORTS
7.1. Introduction
7.2. Results and Discussion
7.2.a. Preparation of 4-chloromethyl 3-nitro PS-BDODMA resin
7.2.b. Preparation of4-aninomethyl 3-nitro PS-BDODMA resin
7.2.c. Preparation of 4-bromomethyl 3-nitre benzamidomethyl PS-BDODMA resin
7.2.d. Preparation of 4-aminomethyl 3-nitro benzamidomethyl PS-BDODMA resin
7.2.e. Preparation of N-alkyl aminomethyl 3 nitro benzamidomethyl PS-BDODMA resin
7.2.f.Synthesis of protected peptide acids, amides and alkyl amides
7.2.g. Mechanism of photolytic cleavage
7.3. Experimental
7.3.a. Preparation of 4-Chloromethyl 3-nitro PS-BDODMA resin
7.3.b. Preparation of 4 Aminomethyl 3-nitro PS-BDODMA resin
7.3.c. Preparation of 4-Bromomethyl benzoic acid
7.3.d. Preparation of 4-Bromomethyl 3-nitro benzoic acid
7.3.e. Preparation of 4-Bromomethyl 3-nitro benzamidomethyl PS-BDODMA resin
7.3.f. Preparation of 4-Aminomethyl 3-nitro benzamidomethyl PS-BDODMA resin
7.3.g. Preparation of 4 -Methyl aminomethyl 3-nitro benzamidomethyl PS-BDODMA resin
7.3.h. Preparation of 4-Ethyl aminomethyl 3-vitro benzamidomethyl PS-BDODMA resin
7.3.i. General synthetic protocol for peptides using solid supports
1. Synthesis of peptides using Boc-amino acids
2. Synthesis of peptides using Fmoc-amino acids
7.3.j. General procedure for photolysis
7.3.k. Synthesis of Boc-NH-Gly-Leu Ala-Leu Ala-Gly, Boc-NH-Leu-Ala Gly-Leu-Ala-Gly, Boc-NH-Gly-Ile-Cys (Acm) -Pro
7.3.l. Synthesis of Fmoc-NH-Ile-Leu Ala-Gly, Fmoc-NH-Leu-Asp (OBu) Leu-Gly-Ala-Gly
7.3.m. Synthesis of Ile Ala-Val-Gly-NH2
7.3.n. Synthesis of Boc-NH-Pro-Val-NH2, Boc-NH-Gly-Phe-Pro-NH2, Boc-Leu-Ala-Gly-Val NH2, Boc-Ala-Gly-Leu-Ile-Gly-NH2
7.3.o. Synthesis of Fmoc-NH Ala-Gly-Leu-Ile-Gly-NHz
7.3.p. Preparation of Boc-NH-Val-N (CH) -resin
7.3.q. Preparation of Boc-NH- ValN (C2H5-resin
7.3.r. Synthesis of Boc-NH-Leu Ala-VaI-NHMe, Boc-NH- Val-LeuAla-Val NHMe, Boc-NH-Val-Leu Ala-ValNHEt, Boc-NH-Leu-Ala-Val-NHEt
Reference
8. SUMMARY AND OUTLOOK