Synthesis, structure and stability of novel dimeric peptide‐disulfides

Leban, Johann; Spaltenstein, Andrew; Landavazo, Antonio; Chestnut, W. G.; Aulabaugh, Ann; Taylor, Lester C. E.; Daniels, Alejandro J.

doi:10.1111/j.1399-3011.1996.tb01340.x

Cited by 4 publications

(1 citation statement)

References 18 publications

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“…Nearly all of the dimeric 18A[A11C] reverted to monomers 1 h after the addition of TCEP, as confirmed by HPLC. Furthermore, upon the addition of the oxidizing agent K 3 Fe(CN) 6 to the 18A[A11C] monomer–POPC nanofibers, 38 scattering was decreased after 9 h, indicating a transition from nanofiber to nanodisc via dimer formation (Figure 8d). Therefore, our results indicate that the morphologies of these nanoassemblies can be controlled by the reduction of the cysteine residue in the 18A[A11C] peptide.…”

Section: Resultsmentioning

confidence: 99%

Nanodisc-to-Nanofiber Transition of Noncovalent Peptide–Phospholipid Assemblies

et al. 2017

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We report a novel molecular architecture of peptide–phospholipid coassemblies. The amphiphilic peptide Ac-18A-NH 2 (18A), which was designed to mimic apolipoprotein α-helices, has been shown to form nanodisc structures with phospholipid bilayers. We show that an 18A peptide cysteine substitution at residue 11, 18A[A11C], forms fibrous assemblies with 1-palmitoyl-2-oleoyl-phosphatidylcholine at a lipid-to-peptide (L/P) molar ratio of 1, a fiber diameter of 10–20 nm, and a length of more than 1 μm. Furthermore, 18A[A11C] can form nanodiscs with these lipid bilayers at L/P ratios of 4–6. The peptide adopts α-helical structures in both the nanodisc and nanofiber assemblies, although the α-helical bundle structures were evident only in the nanofibers, and the phospholipids of the nanofibers were not lamellar. Fluorescence spectroscopic analysis revealed that the peptide and lipid molecules in the nanofibers exhibited different solvent accessibility and hydrophobicity from those of the nanodiscs. Furthermore, the cysteine substitution at residue 11 did not result in disulfide bond formation, although it was responsible for the nanofiber formation, suggesting that this free sulfhydryl group has an important functional role. Alternatively, the disulfide dimer of 18A[A11C] preferentially formed nanodiscs, even at an L/P ratio of 1. Interconversions of these discoidal and fibrous assemblies were induced by the stepwise addition of free 18A[A11C] or liposomes into the solution. Furthermore, these structural transitions could also be induced by the introduction of oxidative and reductive stresses to the assemblies. Our results demonstrate that heteromolecular lipid–peptide complexes represent a novel approach to the construction of controllable and functional nanoscale assemblies.

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Section: Resultsmentioning

confidence: 99%

Nanodisc-to-Nanofiber Transition of Noncovalent Peptide–Phospholipid Assemblies

et al. 2017

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Solid phase synthesis of cyclic peptides: model studies involving i− ( i +4) side chain‐to‐side chain cyclisation

1998

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Conditions for the synthesis of i-(i + 4) side chain-to-side chain head-to-tail Lys-->Glu and Glu-->Lys linked cyclic peptides related to hypoglycaemic analogues of human growth hormone hGH [6-13] have been examined. The success of the cyclisation reaction with the corresponding resin-bound, partially protected linear peptides was found to be both reagent as well as sequence dependent, with competing inter-chain oligomerisation predominating in some cases. The results also indicated that protection with the bulky Fmoc group of the amino acid residues immediately adjacent to the side chain-deprotected Lys and Glu residues, which participate in the cyclisation reaction, enhanced the rate of lactam formation.

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