摘要:

Cyclotides are plant‐derived peptides of approximately 30 amino acids that have the characteristic structural features of a head‐to‐tail cyclized backbone and a cystine knot arrangement of their three conserved disulfide bonds. This article gives a personal account of the discovery of cyclotides, their characterization and their applications, based on work carried out in my laboratory over the last 20 years. It describes some of the background to their discovery and focuses on how their unique structural features lead to exceptional stability. This stability and their amenability to chemical synthesis have made it possible to use cyclotides as templates in protein engineering and drug design applications. These applications complement the interest in cyclotides deriving from their unique structures and natural function as host defense molecules. Copyright © 2013 European Peptide Society and John Wiley&S

ISSN:1075-2617    

DOI:10.1002/psc.2523

年代:2013

数据来源: WILEY

摘要:

The methodology for peptide bond formation is undergoing a continuous evolution where the main actors are being renewed. In recent years, coupling reagents based on the Oxyma scaffold, such as the uronium salt COMU, has been a groundbreaking contribution to the field. The advantages of COMU over classic benzotriazole‐based reagents (HATU, HBTU, HCTU, TBTU) were proven in terms of solubility and coupling efficiency in bulky junctions in our groups and others. However, some aspects of the use of COMU need to be revised and improved, such as the stability of commercial samples in organic solvents, which hampers the compatibility with long synthesis in automated synthesizers. In this review, an overview of the main features and suggestions to improve the use of COMU are presented, along with a discussion on the best conditions for its use in microwave‐assisted peptide robots. Copyright © 2013 European Peptide Society and John Wiley&Sons,

ISSN:1075-2617    

DOI:10.1002/psc.2517

年代:2013

数据来源: WILEY

摘要:

The 2‐(o‐nitrophenyl)‐propyl (NPP) group is used as caging group to mask the nucleobases adenine and cytosine inN‐(2‐aminoethyl)glycine peptide nucleic acids (aeg‐PNA). The adeninyl and cytosinyl nucleo amino acid building blocks Fmoc‐aNPP‐aeg‐OH and Fmoc‐cNPP‐aeg‐OH were synthesized and incorporated into PNA sequences by Fmoc solid phase synthesis relying on high stability of the NPP nucleobase protecting group toward Fmoc‐cleavage, coupling, capping, and resin cleavage conditions. Removal of the nucleobase caging group was achieved by UV‐LED irradiation at 365 nm. The nucleobase caging groups provided sterical crowding effecting the Watson–Crick base pairing, and thereby, the PNA double strand stabilities. Duplex formation can completely be suppressed for complementary PNA containing caging groups in both strands. PNA/PNA recognition can be completely restored by UV light‐triggered release of the photolabile protecting group. Copyright © 2013 European Peptid

ISSN:1075-2617    

DOI:10.1002/psc.2514

年代:2013

数据来源: WILEY

摘要:

A model octapeptide segment derived from vasoactive intestinal peptide (VIP) was utilised to investigate the effect of several conventional cyclisation methods on theα‐helical conformation in short peptide fragments. Three of the classical macrocyclisation techniques (i.e. lactamisation, ring‐closing metathesis and Huisgen cycloaddition) were applied, and the conformations of the resulting cyclic peptides, as well as their linear precursors, were compared by CD analysis. The visibly higher folding propensity of the triazole‐tethered peptide after azide‐alkyne CuAAC macrocyclisation illustrates that the secondary structure of a short peptide fragment can differ significantly depending on the chemical strategy used to covalently cross‐link side chain residues in a ‘helical’ fragment. Copyright © 2013 European Peptide Society and John

ISSN:1075-2617    

DOI:10.1002/psc.2515

年代:2013

数据来源: WILEY

摘要:

The Pictet–Spengler (PS) reaction was performed with various types of substrates: H‐Trp‐OMe and dipeptides with N‐terminal Trp as arylethylamine components and Z‐protected amino aldehydes and peptidoaldehydes as carbonyl components. We found that the C‐terminal part of Trp derivatives did not have any influence on the stereoselectivity of the reaction and the results are the same for simple esters of Trp and dipeptides.On the contrary, the selectivity of the PS reaction with peptidoaldehydes with L configuration of the C‐terminus residue is totally different from that obtained with simple L‐amino aldehydes. It allows us to obtaincisstereoisomers, which cannot be isolated from the reaction with amino aldehydes. But the utility of the peptidoaldehydes as substrates for the PS reaction is reduced by the side formation of enamides which decrease the yield of cyclization. Copyright © 2013 European Peptide Society and John

ISSN:1075-2617    

DOI:10.1002/psc.2516

年代:2013

数据来源: WILEY

摘要:

Alzheimer's disease is characterized by two pathological hallmarks, the intracellular deposition of hyperphosphorylated Tau protein and the extracellular deposition of Aβ1–40/42, both being targets for immunotherapy. This study evaluates the immunogenic properties of three AD‐specific B‐cell epitopes (Tau229–237[pT231/pS235], pyroGluAβ3–8, and Aβ37/38–42/43) linked to five foreign T‐cell epitopes (MVFP, TT, TBC Ag85B, PvT19, and PvT53) by immunizing inbred C57BL/6J (H‐2b), SJL/J (H‐2s2), and C3H/HeN (H‐2k) mice. Two promising candidates with respect to MHC II restriction were selected, and two transgenic mouse models of AD, P301S (H‐2b/k) and Tg2576 (H‐2b/s) animals, were immunized with one B‐cell epitope in combination with two T‐cell epitopes. Responders displayed an enhanced immune response compared with wild‐type animals, which supports the vaccine design and the vaccination strategy. The immune response was also characterized by specific IgG subtype titers, which revealed a strong polarization toward the humoral pathway for immunization of phospho‐Tau, whereas for both Aβvaccines, a mixed cellular/humoral pathway response was observed. Despite the diversity and unpredictability of the immunogenicity of the peptide vaccines, all three peptide vaccine formulations appear to be promising constructs for future evaluation of their therapeutic properties. Copyright © 2013 European Pept

ISSN:1075-2617    

DOI:10.1002/psc.2518

年代:2013

数据来源: WILEY

摘要:

The linear peptide gramicidin A (gA) forms prototypical ion channels specific for monovalent cations and has been extensively used to study the organization and dynamics of membrane channels. This polymorphic peptide can adopt two different types of structures, the helical dimer β6.3 (‘channel state’) and the double helical structure with two intertwined monomers. The structure of gA in micelles of detergent Triton X‐100 has been studied using CD, Fourier transform infrared, and fluorescence spectroscopy. The results obtained demonstrate that only one thermodynamically stable gA structure, the antiparallel left‐handed double helix β5.6, is formed in this membrane‐mimetic environment. The position of the tryptophan fluorescence maximum at 332 nm is the same as that in phospholipid membranes. The causative factors governing the double helix formation in the micellar medium are discussed on the basis of known physicochemical properties of Triton X‐100. Copyright © 2013 European Peptide Society and John

ISSN:1075-2617    

DOI:10.1002/psc.2519

年代:2013

数据来源: WILEY

ISSN:1075-2617    

DOI:10.1002/psc.2521

年代:2013

数据来源: WILEY