Peptide Science Research Papers - Academia.edu (original) (raw)

Ozone-inducible (OI ) peptides found in plants contain repeated sequences consisting of a hexa-repeat unit (YGH GGG) repeated 8–10 times in tandem, and each unit tightly binds copper. To date, the biochemical roles for OI peptides are not... more

Ozone-inducible (OI ) peptides found in plants contain repeated sequences consisting of a hexa-repeat unit (YGH GGG) repeated 8–10 times in tandem, and each unit tightly binds copper. To date, the biochemical roles for OI peptides are not fully understood. Here, we demonstrated that the hexa-repeat unit from OI peptides behaves as metal-binding motif
catalytically active in the superoxide generation. Lastly, possible mechanisms of the reaction and biological consequence of the reactions are discussed by analogy to the action of human prion octarepeat peptides.

To avoid problems arising from the use of the precursor piperidine as a reagent for Fmoc-group removal in solid-phase peptide synthesis (SPPS) several secondary amines were tested as substitutes of piperidine in this reaction. Kinetics of... more

To avoid problems arising from the use of the precursor piperidine as a reagent for Fmoc-group removal in solid-phase peptide synthesis (SPPS) several secondary amines were tested as substitutes of piperidine in this reaction. Kinetics of Fmoc removal as well as manual SPPS yields and by-product formation were compared with piperidine, piperazine, morpholine, pyrrolidine, 4-methyl-piperidine and also their mixtures with DBU used as Fmoc removing reagents. While possessing the same kinetic parameters of Fmoc removal as piperidine, 4-methyl-piperidine was shown to be superior to all tested reagents in terms of the desired product yields. The use of 4-methyl-piperidine in automated SPPS demonstrated its equal efficiency to piperidine in the synthesis process and superiority to piperidine in its behavior in liquid handling modules, i.e., a complete absence of tubing pellets. It makes 4- methyl-piperidine a good substitute for piperidine with no restrictions relevant to the latter as a p...

The sequence-dependent, acid- or base-catalysed aspartimide formation is one of the most serious side reactions in solid-phase synthesis of peptides containing aspartic acid. In the present work, we investigated the susceptibility of... more

The sequence-dependent, acid- or base-catalysed aspartimide formation is one of the most serious side reactions in solid-phase synthesis of peptides containing aspartic acid. In the present work, we investigated the susceptibility of 4-{N-[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methylbutyl]amino}benzyl (Dmab), an aspartic acid β-carboxy side-chain protecting group, for aspartimide formation. As a model, 15-amino acid-residue galanin fragment analogue containing the Asp-Ala motif was used during Fmoc-based solid-phase synthesis. Our study showed a strong tendency of Dmab-protected peptide to form aspartimide with unusual high efficiency. Furthermore, to investigate the susceptibility of Asp-Ala motif for aspartimide formation during the synthesis using Asp(ODmab), a 5-amino acid-residue galanin fragment LGPDA, different types of resin linkers, variety of Fmoc-deprotection conditions and coupling methods were applied. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.

Peptide azides acquired growing impact because of application in bioconjugation via ‘click chemistry’ or Staudinger ligation. Furthermore, there are many methods established in organic synthesis addressing the reduction of azides to... more

Peptide azides acquired growing impact because of application in bioconjugation via ‘click chemistry’ or Staudinger ligation. Furthermore, there are many methods established in organic synthesis addressing the reduction of azides to amines, but no observation of a reductive transformation of peptide azides during SPPS cleavage was yet reported. In the present study, the reduction of peptide azides during SPPS cleavage was investigated depending on the choice of thioscavenger, reacting as reductive species. First observed for short PNA/peptide conjugates the occurring extensive side reaction was also validated for one of the applied azide amino acid building blocks and was further investigated by applying different cleavage cocktails to a series of peptides varying in hydrophobicity and position of the azide moiety in the oligomer sequence. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.

In the present work, we report the synthesis and the characterization of a new chiral nucleoaminoacid, in which a diaminobutyric moiety is connected to the DNA nucleobase by an amidic bond, and its oligomerization to give the... more

In the present work, we report the synthesis and the characterization of a new chiral nucleoaminoacid, in which a diaminobutyric moiety is connected to the DNA nucleobase by an amidic bond, and its oligomerization to give the corresponding nucleo-γ-peptide. The ability of this synthetic polymer to bind complementary DNA was studied in order to explore its possible use in antigene/antisense or diagnostic applications. Our interest in the presented DNA analogue was also supported by the importance of γ-aminoacid-containing compounds in natural products of biological activity and by the known stability of γ-peptides to enzymatic degradation. Furthermore, our work could contribute to the study of the role of nucleopeptides as prebiotic material in a PNA world that could successively lead to the actual DNA/RNA/protein world, as recently assumed. Copyright © 2006 European Peptide Society and John Wiley & Sons, Ltd.

Cystine-knot peptides sharing a common fold but displaying a notably large diversity within the primary structure of flanking loops have shown great potential as scaffolds for the development of therapeutic and diagnostic agents. In this... more

Cystine-knot peptides sharing a common fold but displaying a notably large diversity within the primary structure of flanking loops have shown great potential as scaffolds for the development of therapeutic and diagnostic agents. In this study, we demonstrated that the cystine-knot peptide MCoTI-II, a trypsin inhibitor from Momordica cochinchinensis, can be engineered to bind to cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), an inhibitory receptor expressed by T lymphocytes, that has emerged as a target for the treatment of metastatic melanoma. Directed evolution was used to convert a cystine-knot trypsin inhibitor into a CTLA-4 binder by screening a library of variants using yeast surface display. A set of cystine-knot peptides possessing dissociation constants in the micromolar range was obtained; the most potent variant was synthesized chemically. Successive conjugation with neutravidin, fusion to antibody Fc domain or the oligomerization domain of C4b binding protein resu...

In this study, a novel 18-residue linear antimicrobial peptide derived from the central part of the bovine hemoglobin α-subunit was identified. The peptide was purified by a combination of cationic exchange and reversed-phase... more

In this study, a novel 18-residue linear antimicrobial peptide derived from the central part of the bovine hemoglobin α-subunit was identified. The peptide was purified by a combination of cationic exchange and reversed-phase high-performance liquid chromatography. The sequence was determined to be VNFKLLSHSLLVTLASHL. The theoretical molecular weight of this peptide was calculated to be 1992.38 Da, which is the same as that determined (1992.401 Da) by matrix-assisted laser desorption ionization mass spectrometry. Sequence analysis showed that there is a high degree of homology in this peptide among hemoglobin α-subunits of bovine, sheep, deer, porcine, and human. In a radial-diffusion plate assay, this purified peptide exhibited antimicrobial activity against Escherichia coli, Staphylococcus aureus, and Candida albicans.

The extracellular accumulation of amyloid-beta (Aβ) in neuritic plaques is one of the characteristic hallmarks of Alzheimer's disease (AD), a progressive dementing neurodegenerative disorder of the elderly. By virtue of its structure, Aβ... more

The extracellular accumulation of amyloid-beta (Aβ) in neuritic plaques is one of the characteristic hallmarks of Alzheimer's disease (AD), a progressive dementing neurodegenerative disorder of the elderly. By virtue of its structure, Aβ is able to bind to a variety of biomolecules, including lipids, proteins and proteoglycans. The binding of the various forms of Aβ (soluble or fibrillar) to plasma membranes has been studied with regard to the direct toxicity of Aβ to neurons, and the activation of a local inflammation phase involving microglia.The binding of Aβ to membrane lipids facilitates Aβ fibrillation, which in turn disturbs the structure and function of the membranes, such as membrane fluidity or the formation of ion channels.A subset of membrane proteins binds Aβ. The serpin-enzyme complex receptor (SEC-R) and the insulin receptor can bind the monomeric form of Aβ. The α7nicotinic acetylcholine receptor (α7nAChR), integrins, RAGE (receptor for advanced glycosylation end-products) and FPRL1 (formyl peptide receptor-like 1) are able to bind the monomeric and fibrillar forms of Aβ. In addition, APP (amyloid precursor protein), the NMDA-R (N-methyl-D-aspartate receptor), the P75 neurotrophin receptor (P75NTR), the CLAC-P/collagen type XXV (collagen-like Alzheimer amyloid plaque component precursor/collagen XXV), the scavenger receptors A, BI (SR-A, SR-BI) and CD36, a complex involving CD36, α6β1–integrin and CD47 have been reported to bind the fibrillar form of Aβ.Heparan sulfate proteoglycans have also been described as cell-surface binding sites for Aβ. The various effects of Aβ binding to these membrane molecules are discussed. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd.

Thermally induced phase transformation in bioorganic nanotubes, which self-assembled from two ultrashort dipeptides of different origin, aromatic diphenylalanine (FF) and aliphatic dileucine (LL), is studied. In both FF and LL nanotubes,... more

Thermally induced phase transformation in bioorganic nanotubes, which self-assembled from two ultrashort dipeptides of different origin, aromatic diphenylalanine (FF) and aliphatic dileucine (LL), is studied. In both FF and LL nanotubes, irreversible phase transformation found at 120-180 °C is governed by linear-to-cyclic dipeptide molecular modification followed by formation of extended β-sheet structure. As a result of this process, native open-end FF and LL nanotubes are transformed into ultrathin nanofibrils. Found deep reconstructions at all levels from macroscopic (morphology) and structural space symmetry to molecular give rise to new optical properties in both aromatic FF and aliphatic LL nanofibrils and generation of blue photoluminescence (PL) emission. It is shown that observed blue PL peak is similar in these supramolecular nanofibrillar structures and is excited by the network of non-covalent hydrogen bonds that link newly thermally induced neighboring cyclic dipeptide ...

Structural modification of the peptide backbone via N-methylation is a powerful tool to modulate the pharmacokinetic profile and biological activity of peptides. Here we describe a rapid and highly efficient microwave(MW)-assisted... more

Structural modification of the peptide backbone via N-methylation is a powerful tool to modulate the pharmacokinetic profile and biological activity of peptides. Here we describe a rapid and highly efficient microwave(MW)-assisted Fmoc/tBu solid-phase method to prepare short chain N-methyl-rich peptides, using Rink amide p-methylbenzhydrylamine (MBHA) resin as solid-phase support. This method produces peptides in high yield and purity, and reduces the time required for Fmoc-N-methyl amino acid coupling. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.

In the present work, we report the synthesis and the characterization of dab PNA hexamers with diaminobutyric acid backbone of D- or/and L-configuration. In particular, the four nucleo-amino acids we synthesized, D- and L-diaminobutyryl... more

In the present work, we report the synthesis and the characterization of dab PNA hexamers with diaminobutyric acid backbone of D- or/and L-configuration. In particular, the four nucleo-amino acids we synthesized, D- and L-diaminobutyryl adenines and D- and L-diaminobutyryl thymines, were used in various combinations to assemble the following oligomers: H-G-(t L−dab)6-K-NH2, H-G-(t D−dab)6-K-NH2, H-G-(a L−dab)6-K-NH2, H-G-(t L−dab-t D−dab)3-K-NH2, H-G-(a L−dab-a D−dab)3-K-NH2, H-G-(a L−dab-t D−dab)3-K-NH2. By using CD and UV spectroscopies, we investigated the ability of complementary dab PNA strands to bind to each other. We found that binding occurs only between oligomers with backbone of alternate configuration [(t L−dab-t D−dab)3/(a L−dab-a D−dab)3 and (a L−dab-t D−dab)3/(a L−dab-t D−dab)3] and implies cooperative hydrogen bonds and base stacking. Furthermore, interesting properties relative to the self-complementary oligomer (a L−dab-t D−dab)3 forming palindromic complexes emerged from preliminary dynamic light-scattering experiments that suggested the formation of multimeric aggregates. These results, together with the high serum stability of the DABA-based oligomers, as shown by HPLC analysis, encourage us to further study dab PNAs as new self-recognizing bio-inspired polymers, to develop new nanomaterials in biotechnological and biomedical applications. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.