Application of Microwave Irradiation to the Synthesis of 14-Helical β-Peptides

Murray, Justin K.; Gellman, Samuel H.

doi:10.1021/ol0501727

Cited by 101 publications

(98 citation statements)

References 31 publications

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“…␣-Peptide 1 and ␣/␤-Peptides 2-5 were prepared by standard Fmoc automated solid phase synthesis. ␣/␤-Peptides 6-9 were prepared by microwave-assisted Fmoc solid-phase peptide synthesis (36,37). Detailed synthetic methods can be found in SI Text.…”

Section: Methodsmentioning

confidence: 99%

Interplay among side chain sequence, backbone composition, and residue rigidification in polypeptide folding and assembly

Horne

Price

Gellman

2008

Proc. Natl. Acad. Sci. U.S.A.

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114

151

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The extent to which polypeptide conformation depends on side-chain composition and sequence has been widely studied, but less is known about the importance of maintaining an α-amino acid backbone. Here, we examine a series of peptides with backbones that feature different repeating patterns of α- and β-amino acid residues but an invariant side-chain sequence. In the pure α-backbone, this sequence corresponds to the previously studied peptide GCN4-pLI, which forms a very stable four-helix bundle quaternary structure. Physical characterization in solution and crystallographic structure determination show that a variety of α/β-peptide backbones can adopt sequence-encoded quaternary structures similar to that of the α prototype. There is a loss in helix bundle stability upon β-residue incorporation; however, stability of the quaternary structure is not a simple function of β-residue content. We find that cyclically constrained β-amino acid residues can stabilize the folds of α/β-peptide GCN4-pLI analogues and restore quaternary structure formation to backbones that are predominantly unfolded in the absence of cyclic residues. Our results show a surprising degree of plasticity in terms of the backbone compositions that can manifest the structural information encoded in a sequence of amino acid side chains. These findings offer a framework for the design of nonnatural oligomers that mimic the structural and functional properties of proteins.

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Section: Methodsmentioning

confidence: 99%

Interplay among side chain sequence, backbone composition, and residue rigidification in polypeptide folding and assembly

Horne

Price

Gellman

2008

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

114

151

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“…microwave (MW) irradiation has become a preferred choice for the organic chemist [1,[14][15][16]. There are many examples of the application of MW irradiation in peptide synthesis, including automated peptide synthesizers equipped with MW capability [17][18][19][20][21][22]. The main advantages of MW-assisted chemistry are shorter reaction times and higher yields.…”

Section: Introductionmentioning

confidence: 99%

Aqueous Microwave-Assisted Solid-Phase Synthesis Using Boc-Amino Acid Nanoparticles

et al. 2013

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Abstract:We have previously developed water-based microwave (MW)-assisted peptide synthesis using Fmoc-amino acid nanopaticles. It is an organic solvent-free, environmentally friendly method for peptide synthesis. Here we describe water-based MW-assisted solid-phase synthesis using Boc-amino acid nanoparticles. The microwave irradiation allowed rapid solid-phase reaction of nanoparticle reactants on the resin in water. We also demonstrated the syntheses of Leu-enkephalin, Tyr-Gly-Gly-Phe-Leu-OH, and difficult sequence model peptide, Val-Ala-Val-Ala-Gly-OH, using our water-based MW-assisted protocol with Boc-amino acid nanoparticles.

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“…Further studies revealed that β-peptides enter HeLa cells via a dynamin-independent, ameloride-sensitive endocytotic entry mechanism similar to macropinocytosis. While both polyproline type II helices and β-peptides achieve the goal of cell permeability, the latter possesses the advantage of small size (MW, P14LRR = 2979 Da; Gellman β-peptide decamer 1 = 1485 Da) as well as demonstrated compatibility with microwave synthesis [17]. In addition, the synthesis of β 3 -amino acid monomers [18] is more straightforward than the pre-decoration of hydroxyproline.…”

Section: Introductionmentioning

confidence: 99%

Sophistication of foldamer form and function in vitro and in vivo

Bautista

Craig

Harker

et al. 2007

Current Opinion in Chemical Biology

142

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SummaryAdvances in the foldamer field in recent years are as diverse as the backbones of which they are composed. Applications have ranged from cellular penetration and membrane disruption to discrete molecular recognition, while efforts to control the complex geometric shape of foldamers has entered the realm of tertiary and quaternary structure. This review will provide recent examples of progress in the foldamer field, highlighting the significance of this class of compounds and the advances that have been made towards exploiting their full potential.

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Application of Microwave Irradiation to the Synthesis of 14-Helical β-Peptides

Cited by 101 publications

References 31 publications

Interplay among side chain sequence, backbone composition, and residue rigidification in polypeptide folding and assembly

Interplay among side chain sequence, backbone composition, and residue rigidification in polypeptide folding and assembly

Aqueous Microwave-Assisted Solid-Phase Synthesis Using Boc-Amino Acid Nanoparticles

Sophistication of foldamer form and function in vitro and in vivo

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