- Mimicking of Arginine by Functionalized Nω-Carbamoylated Arginine As a New Broadly Applicable Approach to Labeled Bioactive Peptides: High Affinity Angiotensin, Neuropeptide Y, Neuropeptide FF, and Neurotensin Receptor Ligands As Examples
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Derivatization of biologically active peptides by conjugation with fluorophores or radionuclide-bearing moieties is an effective and commonly used approach to prepare molecular tools and diagnostic agents. Whereas lysine, cysteine, and N-terminal amino acids have been mostly used for peptide conjugation, we describe a new, widely applicable approach to peptide conjugation based on the nonclassical bioisosteric replacement of the guanidine group in arginine by a functionalized carbamoylguanidine moiety. Four arginine-containing peptide receptor ligands (angiotensin II, neurotensin(8-13), an analogue of the C-terminal pentapeptide of neuropeptide Y, and a neuropeptide FF analogue) were subject of this proof-of-concept study. The Nω-carbamoylated arginines, bearing spacers with a terminal amino group, were incorporated into the peptides by standard Fmoc solid phase peptide synthesis. The synthesized chemically stable peptide derivatives showed high receptor affinities with Ki values in the low nanomolar range, even when bulky fluorophores had been attached. Two new tritiated tracers for angiotensin and neurotensin receptors are described.
- Keller, Max,Kuhn, Kilian K.,Einsiedel, Jürgen,Hübner, Harald,Biselli, Sabrina,Mollereau, Catherine,Wifling, David,Svobodová, Jaroslava,Bernhardt, Günther,Cabrele, Chiara,Vanderheyden, Patrick M. L.,Gmeiner, Peter,Buschauer, Armin
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Read Online
- Antimicrobial analogues of gramicidin S
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Disclosed herein are N-aminated variants of Gramicidin S and methods of using the same for treating infections in a subject.
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Page/Page column 29; 30
(2019/07/29)
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- Assessing the ability of a short fluorinated antifreeze glycopeptide and a fluorinated carbohydrate derivative to inhibit ice recrystallization
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A short fluorinated antifreeze glycopeptide (2) was synthesized and evaluated for ice recrystallization inhibition (IRI) activity. The activity of 2 was compared to native biological antifreeze AFGP 8 and a rationally designed C-linked AFGP analogue (OGG-Gal, 1). In addition, a simple fluorinated galactose derivative was prepared and its IRI activity was compared to non-fluorinated compounds. The results from this study suggest that the stereochemistry at the anomeric position in the carbohydrate plays a role in imparting ice recrystallization inhibition activity and that incorporation of hydrophobic groups such as fluorine atoms cause a decrease in IRI activity. These observations are consistent with the theory that fluorine atoms increase ordering of bulk water resulting in a decrease of IRI activity, supporting our previously proposed mechanism of ice recrystallization inhibition.
- Chaytor, Jennifer L.,Ben, Robert N.
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supporting information; experimental part
p. 5251 - 5254
(2010/10/02)
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- Lanthanide(III) complexes with two hexapeptides incorporating unnatural chelating amino acids: Secondary structure and stability
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Unnatural metal-chelating amino acids bearing aminodiacetate side-chains have been introduced into two hexapeptides to obtain efficient lanthanide-binding peptides. The synthesis of the enantiopure Fmoc-Ada.,(tBu)2-OH synthons is described with overall yields of 32 and 50% for n = 2 and n = 3 side-chain carbon atoms, respectively. The two peptides AcWAdanPGAdanGNH2 (Pn) were synthesized from the protected synthons by standard solid-phase peptide synthesis. Studies of the lanthanide complexes of the two peptides P" by luminescence titrations, mass spectrometry, circular dichroism, and solution NMR spectroscopy demonstrate that the Ada., chain length has a dramatic effect on the complexation properties. Indeed, the flexible compound P3 forms a mononuclear complex of moderate stability (β11 = 10 9.9), which tends to transform into a binuclear species in the presence of excess of the metal ion. Interestingly, the more compact peptide P2 provides stable Ln3+ complexes with the exclusive formation of the mononuclear LnP2 adduct. The stability constant of TbP2 is two orders of magnitude higher (β11 = 10 12.1) than that measured for P3. The 800 MHz NMR spectrum of the La3+ complex of P2 evidences a well-defined type II ss-turn as well as a hydrophobic Trp(indole)-Pro interaction. These interactions exemplify the non-innocent character of the peptide spacer in the complex LaP2 as well as the role of a peptide secondary structure in the stabilization of metal complexes.
- Cisnetti, Federico,Gateau, Christelle,Lebrun, Colette,Delangle, Pascale
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scheme or table
p. 7456 - 7469
(2010/03/24)
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- Oppolzer sultam directed aldol as a key step for the stereoselective syntheses of antitumor antibiotic belactosin C and its synthetic congeners
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An efficient protocol has been developed using D-(2R)-Oppolzer sultam as a chiral auxiliary for generating anti/syn diastereomers with high enantiopurity and utilized in the efficient synthesis of natural product belactosin C and their synthetic congeners
- Kumaraswamy, Gullapalli,Padmaja, Mogilisetti,Markondaiah, Bekkam,Jena, Nivedita,Sridhar, Balasubramanian,Kiran, Marelli Udaya
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p. 337 - 340
(2007/10/03)
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- Enantioselective total syntheses of belactosin A, belactosin C, and its homoanalogue
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Enantioselective total syntheses of belactosin A, belactosin C, and its homoanalogue have been accomplished in high overall yields (32% for belactosin A from the amino acid 10, and 35 and 36% for belactosin C and its homoanalogue, respectively). This conc
- Larionov, Oleg V.,De Meijere, Armin
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p. 2153 - 2156
(2007/10/03)
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