Abstract
Poly(N,N-bisethylamine) dendrimers with high content of poly(ethylene glycol) were synthesized on 3-(Acryloyloxy)-2-hydroxypropylmethacrylate-crosslinked polystyrene (PS-AHMA) resin and tested in various conditions of solid phase peptide synthesis. The dendritic templates were generated to the second generation on cross-linker active site of 3-(Acryloyloxy)-2-hydroxypropylmethacrylate (AHMA). First generation dendrimer was designed by series of four-stage reactions, such as Schiff base incorporation, acidolytic cleavage, diazotization and thionyl chloride treatment and same synthetic routes were followed for second generation also. Poly(ethylene glycol) (PEG1000) has been grafted to second-generation dendrimer and used to check various physico-chemical parameters in Fmoc/Boc peptide synthetic conditions. The utility of PEGylated dendrimer support was demonstrated by synthesizing biologically potent linear as well as disulfide-bonded peptide by Fmoc method.
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References
Auzanneau FI, Meldal M, Bock K (1995) Synthesis, characterization and biocompatibility of PEGA resins. J Pept Sci 1:31–44
Coin I, Beyermann M, Bienert M (2007) Solid-phase peptide synthesis: from standard procedures to the synthesis of difficult sequences. Nat Prot 2:3247–3256
Dolle RE, Bourdonnec BL, Morales GA, Moriarty KJ, Salvino JM (2005) Comprehensive survey of combinatorial library synthesis. J Comb Chem 8:597–635
Galande AK, Weissleder R, Tung C (2005) An effective method of on-resin disulfide bond formation in peptides. J Comb Chem 7:174–177
Geysen HM, Schoenen F (2003) Combinatorial compound libraries for drug discovery: an ongoing challenge. Nat Rev Drug Discov 2:222–230
Gooding OW, Baudart S, Deegen TL, Heisler K, Labadie JW, Newcomeb WS, Porco JA Jr, van Eikeren P (1999) On the development of new poly(styrene-oxyethylene) graft copolymer resin supports for solid-phase organic synthesis. J Comb Chem 1:113–122
Groth T, Grotli M, Meldal M (2001) Diffusion of reagents in macrobeads. J Comb Chem 3:461–468
Guyot A, Bartholin M (1982) Design and properties of polymers as materials for fine chemistry. Prog in Polym Sci 8:277–331
Jacob MK, Leena S, Kumar KS (2008) Peptide-polymer biotherapeutic synthesis on novel cross-linked beads with ‘‘spatially tunable’’ and ‘‘isolated’’ functional sites. Biopolymers 90:512–525
Krishnakumar IM, Mathew B (2002) A comparison of rigid and flexible cross-linked polymer-supported peptide synthesis. Eur Poly J 38:1745–1752
Kumar GSV, Leena S, Kumar KS (2004) Synthesis of a shark repellent peptide toxin, pardaxin (16–33) on a highly flexible polymer support: Clpser. Prot Pep Lett 11:547–554
Labadie JW (1998) Polymeric supports for solid phase synthesis. Curr Opin Chem Biol 2:346–352
Lu YA, Felix AM (1994) Pegylated peptides III. Solid-phase synthesis with pegylating reagents of varying molecular weight: synthesis of multiply pegylated peptides. React Polym 22:221–229
Merrifield RB (1963) Solid phase peptide synthesis. I. The synthesis of a tetrapeptide. J Am Chem Soc 85:2149–2153
Pierre TN, Seon AA, Amiche M, Nicolas P (2003) Phylloxin, a novel peptide antibiotic of the dermaseptin family of antimicrobial/opioid peptide precursors. Eur J Biochem 267:370–378
Rademann J, Grotli M, Meldal M, Bock K (1999) SPOCC: a resin for solid-phase organic chemistry and enzymatic reactions on solid phase. J Am Chem Soc 121:5459–5466
Rapp w, Zhang L, Bayer E, In: Epton R (ed) (2002) Innovations and perspectives in solid phase synthesis. SPCC, Birmingham, pp 205–210
Roberts M, Bentley M, Harris JM (2002) Chemistry for peptide and protein PEGylation. Adv Drug Del Rev 54:459–476
Roice M, Pillai VNR (2005) Poly(styrene-co-glycerol dimethacrylate): synthesis, characterization, and application as a resin for gel-phase peptide synthesis. J Polym Sci, Part A: Polym Chem 43:4382–4392
Schleyer A, Meldal M, Renil M, Paulsen H, Bock K (1997) Direct solid-phase glycosylations of peptide templates on a novel PEGbased resin. Angew Chem Int Ed Engl 36:1976–1978
Siyad MA, Kumar GSV (2012a) SPED-(styrene-polyethyleneglycol diacrylate-9-decen-1-ol): a novel resin for solid phase peptide synthesis; synthesis and characterization of biologically potent endothelin classes of peptides. Comb Chem High Throughput Screen 15:386–394
Siyad MA, Kumar GSV (2012b) Synthesis, characterization, and evaluation of PS-PPDC resin: a novel flexible cross-linked polymeric support for solid-phase organic synthesis. Biopolymers 98:239–248
Siyad MA, Nair ASV, Kumar GSV (2010) Solid-phase peptide synthesis of endothelin receptor antagonists on novel flexible, styrene-acryloyloxyhydroxypropyl methacrylate tripropyleneglycoldiacrylate [SAT] resin. J Comb Chem 12:298–305
Wang Z, Yang RL (2010) PEG-related polymer resins as synthetic supports. Sci China Chem 53:1844–1852
Wang YA, Zhang G, Yan H, Fan Y, Shi Z, Lu Y, Sun Q, Jiang W, Zheng Y, Li S, Liu Z (2006) Polystyrene resins cross-linked with di- or tri(ethylene glycol) dimethacrylates as supports for solid-phase peptide synthesis. Tetrahedron 62:4948–4953
Zalipsky S, Chang JL, Albericio F, Barany G (1994) Preparation and applications of polyethylene glycol-polystyrene graft resin supports for solid-phase peptide synthesis. React Polym 22:243–258
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The authors acknowledge the CSIR, New Delhi, for providing funding and RGCB for research facilities. The help rendered by IISc, Bangalore, for NMR and MALDI facilities is gratefully acknowledged.
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Siyad, M.A., Vinod Kumar, G.S. PEGylated dendrimer polystyrene support: synthesis, characterisation and evaluation of biologically active peptides. Amino Acids 44, 947–959 (2013). https://doi.org/10.1007/s00726-012-1424-6
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DOI: https://doi.org/10.1007/s00726-012-1424-6