Propargyloxyproline Regio- and Stereoisomers for Click-Conjugation of Peptides: Synthesis and Application in Linear and Cyclic Peptides

2015 ◽  
Vol 68 (9) ◽  
pp. 1365 ◽  
Author(s):  
Susan E. Northfield ◽  
Simon J. Mountford ◽  
Jerome Wielens ◽  
Mengjie Liu ◽  
Lei Zhang ◽  
...  
Keyword(s):  
Peptide Synthesis ◽  
Cyclic Peptides ◽  
Click Reaction ◽  
Fluorescent Labels ◽  
Peptide Conjugates ◽  
Conformational Properties ◽  
Peptides Synthesis

The use of the click reaction for the introduction of conjugate groups, such as affinity or fluorescent labels, to a peptide for the study of peptide biochemistry and pharmacology is widespread. However, the nature and location of substituted 1,2,3-triazoles in peptide sequences may markedly affect conformation or binding as compared with native sequences. We have examined the preparation and application of propargyloxyproline (Pop) residues as a precursor to such peptide conjugates. Pop residues are available in a range of regio- and stereoisomers from hydroxyproline precursors and are readily prepared in Fmoc-protected form. They can be incorporated routinely in peptide synthesis and broadly retain the conformational properties of the parent proline containing peptides. This is exemplified by the preparation of biotin- and fluorophore-labelled peptides derived from linear and cyclic peptides.

scholarly journals Click Conjugation of Boron Dipyrromethene (BODIPY) Fluorophores to EGFR-Targeting Linear and Cyclic Peptides

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 593 ◽  
Author(s):  
Tyrslai M. Williams ◽  
Nichole E. M. Kaufman ◽  
Zehua Zhou ◽  
Sitanshu S. Singh ◽  
Seetharama D. Jois ◽  
...  
Keyword(s):  
Cyclic Peptides ◽  
Cyclic Peptide ◽  
Click Reaction ◽  
Cycloaddition Reaction ◽  
Growth Factor Receptor ◽  
Extracellular Domain ◽  
Binding Studies ◽  
Peptide Conjugates ◽  
Human Carcinoma

Through a simple 1,3-cycloaddition reaction, three BODIPY-peptide conjugates that target the extracellular domain of the epidermal growth factor receptor (EGFR) were prepared and their ability for binding to EGFR was investigated. The peptide ligands K(N3)LARLLT and its cyclic analog cyclo(K(N3)larllt, previously shown to have high affinity for binding to the extracellular domain of EGFR, were conjugated to alkynyl-functionalized BODIPY dyes 1 and 2 via a copper-catalyzed click reaction. This reaction produced conjugates 3, 4, and 5 in high yields (70–82%). In vitro studies using human carcinoma HEp2 cells that overexpress EGFR demonstrated high cellular uptake, particularly for the cyclic peptide conjugate 5, and low cytotoxicity in light (~1 J·cm−2) and darkness. Surface plasmon resonance (SPR) results show binding affinity of the three BODIPY-peptide conjugates for EGFR, particularly for 5 bearing the cyclic peptide. Competitive binding studies using three cell lines with different expressions of EGFR show that 5 binds specifically to EGFR-overexpressing colon cancer cells. Among the three conjugates, 5 bearing the cyclic peptide exhibited the highest affinity for binding to the EGFR protein.

scholarly journals Conformational properties of N-acetyl-N-methyl-alpha,beta-dehydroalanine N'-methylamide.

2006 ◽  
Vol 53 (1) ◽  
pp. 227-232 ◽  
Author(s):  
Agnieszka Macedowska ◽  
Dawid Siodłak ◽  
Barbara Rzeszotarska
Keyword(s):  
Cyclic Peptides ◽  
Conformational Flexibility ◽  
Biological Action ◽  
Torsion Angles ◽  
Dehydroamino Acids ◽  
Theoretical Methods ◽  
Conformational Properties ◽  
Alpha Beta

The conformational properties of Ac-Delta(Me)Ala-NHMe (N-acetyl-N-methyl-alpha,beta-dehydroalanine N'-methylamide), as the simplest model of N-methyl-alpha,beta-dehydroamino acids, was examined with theoretical methods and in comparison with Ac-DeltaAla-NHMe and Ac-DeltaAla-NMe(2). The N-terminal amide of the Delta(Me)Ala residue easily adopts the configuration cis and the torsion angles phi, psi are highly flexible. The Delta(Me)Ala residue is a conformational flexibilizer as compared to the parent DeltaAla, which is a conformational stiffener. This seems to be the reason why Delta(Me)Ala is found in small natural cyclic peptides, where it ensures the conformational flexibility necessary for biological action.

scholarly journals Utilizing Copper-Mediated Deprotection of Selenazolidine for Cyclic Peptides Synthesis

2019 ◽  
Author(s):  
Zhenguang Zhao ◽  
Norman Metanis
Keyword(s):  
Chemical Synthesis ◽  
Cyclic Peptides ◽  
One Pot ◽  
Oxidative Folding ◽  
Peptides Synthesis

<p>Selenazoliline (Sez) was originally developed as a masking form of selenocysteine (Sec) for the chemical synthesis of challenging proteins. Here we utilize Sez and our recent reported copper(II)-mediated deprotection for the synthesis of cyclic peptides. This approach allows deprotection, cyclization and deselenization in one-pot, providing several different cyclic peptides in good yields. In addition, the Sec can also be retained, which enhance the oxidative folding of disulfide-rich cyclic proteins, such as the case of Kalata S. </p>

scholarly journals Utilizing Copper-Mediated Deprotection of Selenazolidine for Cyclic Peptides Synthesis

2019 ◽  
Author(s):  
Zhenguang Zhao ◽  
Norman Metanis
Keyword(s):  
Chemical Synthesis ◽  
Cyclic Peptides ◽  
One Pot ◽  
Oxidative Folding ◽  
Peptides Synthesis

<p>Selenazoliline (Sez) was originally developed as a masking form of selenocysteine (Sec) for the chemical synthesis of challenging proteins. Here we utilize Sez and our recent reported copper(II)-mediated deprotection for the synthesis of cyclic peptides. This approach allows deprotection, cyclization and deselenization in one-pot, providing several different cyclic peptides in good yields. In addition, the Sec can also be retained, which enhance the oxidative folding of disulfide-rich cyclic proteins, such as the case of Kalata S. </p>

A critical assessment of force field accuracy against NMR data for cyclic peptides containing β-amino acids

2018 ◽  
Vol 20 (23) ◽  
pp. 15807-15816 ◽  
Author(s):  
C. Paissoni ◽  
F. Nardelli ◽  
S. Zanella ◽  
F. Curnis ◽  
L. Belvisi ◽  
...  
Keyword(s):  
Amino Acids ◽  
Force Field ◽  
Cyclic Peptides ◽  
Force Fields ◽  
Critical Assessment ◽  
Isoaspartic Acid ◽  
Nmr Parameters ◽  
Nmr Data ◽  
Conformational Properties

A critical assessment of the reproducibility of NMR parameters of β amino acids pinpoints the major weaknesses of eight widely used force fields in reproducing the equilibrium conformational properties of highly constrained cyclic peptides containing isoAspartic acid.

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