scholarly journals Solid-phase peptide synthesis: an overview focused on the preparation of biologically relevant peptides

RSC Advances ◽  
2014 ◽  
Vol 4 (62) ◽  
pp. 32658-32672 ◽  
Author(s):  
Jose M. Palomo
Keyword(s):  
Amino Acids ◽  
Posttranslational Modifications ◽  
Unnatural Amino Acids ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Peptide Sequence ◽  
Biologically Relevant ◽  
Biological Studies ◽  
Exceptional Value ◽  
Short Time

Tailor-made design preparation of complex peptide sequence including posttranslational modifications, fluorescent labels, unnatural amino acids are of exceptional value for biological studies of several important diseases. The possibility to obtain these molecules in sufficient amounts in relative short time is thanks to the solid-phase approach.

scholarly journals Peptidomimetic Modulators of BACE1

2020 ◽  
Vol 73 (4) ◽  
pp. 366
Author(s):  
John Paul Juliano ◽  
David H. Small ◽  
Marie-Isabel Aguilar
Keyword(s):  
Amino Acids ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Amyloid Β ◽  
Amino Acid Sequences ◽  
Peptide Sequence ◽  
Fluorescent Substrate ◽  
Double Mutation ◽  
Affinity Peptide ◽  
Inhibition Potency

The β-site APP Cleaving enzyme 1 (BACE1) is a membrane-associated aspartyl protease which mediates the production of amyloid-β (Aβ), a major component of amyloid plaques in the Alzheimer’s disease brain. We have synthesised and characterised a series of peptidomimetic analogues of BACE substrates that incorporate two distinct stabilising structures. To demonstrate the potential activity of these compounds, a variety of assaying strategies were used to investigate cleavage susceptibility and inhibition potency under competitive and non-competitive conditions. β-Amino acids and scissile site N-methylation were incorporated into peptide substrate templates as transition state isostere (TSI) substitutes by positional scanning to generate series of non-TSI β-peptidomimetics. The amino acid sequences flanking the β-cleavage site within APP carrying the Swedish double mutation (APPSW), Neuregulin, the synthetic hydroxyethylene-based TSI peptide inhibitor OM99-2, and the high affinity peptide sequence SEISYEVEFR, served as the four substrate templates from which over 60 peptides were designed and synthesised by solid phase peptide synthesis. A quenched fluorescent substrate BACE1 assay in conjunction with liquid chromatography–mass spectrometry (LC-MS) analysis was established to investigate cleavage susceptibility and inhibition potency under competitive and non-competitive conditions. It was determined that β-amino acids substituted at the P1 scissile site position within known peptide substrates were resistant to proteolysis, and particular substitutions induced a concentration-dependent stimulation of BACE1, indicating a possible modulatory role of native BACE1 substrates.

scholarly journals Synthesis of Fmoc-Triazine Amino Acids and Its Application in the Synthesis of Short Antibacterial Peptidomimetics

2020 ◽  
Vol 21 (10) ◽  
pp. 3602
Author(s):  
Pethaiah Gunasekaran ◽  
Eun Young Kim ◽  
Jian Lee ◽  
Eun Kyoung Ryu ◽  
Song Yub Shin ◽  
...  
Keyword(s):  
Amino Acids ◽  
Peptide Synthesis ◽  
Unnatural Amino Acids ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Proteolytic Degradation ◽  
Antibacterial Resistance ◽  
Hydrophobic Residues ◽  
Intracellular Targeting ◽  
Proteolytic Stability

To combat the escalating rise of antibacterial resistance, the development of antimicrobial peptides (AMPs) with a unique mode of action is considered an attractive strategy. However, proteolytic degradation of AMPs remains the greatest challenge in their transformation into therapeutics. Herein, we synthesized Fmoc-triazine amino acids that differ from each other by anchoring either cationic or hydrophobic residues. These unnatural amino acids were adopted for solid-phase peptide synthesis (SPPS) to synthesize a series of amphipathic antimicrobial peptidomimetics. From the antimicrobial screening, we found that the trimer, BJK-4 is the most potent short antimicrobial peptidomimetic without showing hemolytic activity and it displayed enhanced proteolytic stability. Moreover, the mechanism of action to kill bacteria was found to be an intracellular targeting.

ChemInform Abstract: 4-Methoxybenzyloxycarbonyl Amino Acids in Solid Phase Peptide Synthesis.

ChemInform ◽  
1988 ◽  
Vol 19 (16) ◽  
Author(s):  
S. S. WANG ◽  
S. T. CHEN ◽  
K. T. WANG ◽  
R. B. MERRIFIELD
Keyword(s):  
Amino Acids ◽  
Peptide Synthesis ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis

scholarly journals On-Resin Strategy to Label α-Conotoxins: Cy5-RgIA, a Potent α9α10 Nicotinic Acetylcholine Receptor Imaging Probe

2020 ◽  
Vol 73 (4) ◽  
pp. 327
Author(s):  
Markus Muttenthaler ◽  
Simon T. Nevin ◽  
Marco Inserra ◽  
Richard J. Lewis ◽  
David J. Adams ◽  
...  
Keyword(s):  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Resonance Energy ◽  
Peptide Sequence ◽  
Hill Coefficient ◽  
Receptor Imaging ◽  
Nicotinic Acetylcholine ◽  
Site Specific

In-solution conjugation is the most commonly used strategy to label peptides and proteins with fluorophores. However, lack of site-specific control and high costs of fluorophores are recognised limitations of this approach. Here, we established facile access to grams of Cy5-COOH via a two-step synthetic route, demonstrated that Cy5 is stable to HF treatment and therefore compatible with tert-butyloxycarbonyl solid phase peptide synthesis (Boc-SPPS), and coupled Cy5 to the N-terminus of α-conotoxin RgIA while still attached to the resin. Folding of the two-disulfide containing Cy5-RgIA benefitted from the hydrophobic nature of Cy5, resulting in only the globular disulfide bond isomer. In contrast, wild-type α-RgIA folded into the inactive ribbon and bioactive globular isomer under the same conditions. Labelled α-RgIA retained its ability to inhibit acetylcholine (100µM)-evoked current reversibly with an IC50 of 5.0nM (Hill coefficient=1.7) for Cy5-RgIA and an IC50 of 1.6 (Hill coefficient=1.2) for α-RgIA at the α9α10 nicotinic acetylcholine receptor (nAChR) heterologously expressed in Xenopus oocytes. Cy5-RgIA was then used to successfully visualise nAChRs in the RAW264.7 mouse macrophage cell line. This work introduced not only a new and valuable nAChR probe, but also a new versatile synthetic strategy that facilitates production of milligram to gram quantities of fluorophore-labelled peptides at low cost, which is often required for invivo experiments. The strategy is compatible with Boc- and 9-fluorenylmethoxycarbonyl (Fmoc)-chemistry, allows site-specific labelling of free amines anywhere in the peptide sequence, and can also be used for the introduction of Cy3/Cy5 fluorescence resonance energy transfer (FRET) pairs.

On the use of s-t-butylsulphenyl group for protection of cysteine in solid-phase peptide synthesis using fmoc-amino acids

Tetrahedron ◽  
1987 ◽  
Vol 43 (12) ◽  
pp. 2675-2680 ◽  
Author(s):  
Ramon Eritja ◽  
J.Paige Ziehler-Martin ◽  
Peter A. Walker ◽  
Terry D. Lee ◽  
Kassu Legesse ◽  
...  
Keyword(s):  
Amino Acids ◽  
Peptide Synthesis ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis

Solid-phase peptide synthesis using Nα-trityl-amino acids

2001 ◽  
Vol 8 (6) ◽  
pp. 331-338
Author(s):  
Beatriz G. de la Torre ◽  
Miguel A. Marcos ◽  
Ramon Eritja ◽  
Fernando albericio
Keyword(s):  
Amino Acids ◽  
Peptide Synthesis ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis
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