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Metal chelates targeted to amyloid peptides are widely explored as diagnostic tools or therapeutic agents. The attachment of a metal complex to amyloid recognition units typically leads to a decrease in peptide affinity. We show here that by separating a macrocyclic GdL chelate and a PiB targeting unit with a long hydrophobic C10 linker, it is possible to attain nanomolar affinities for both Aβ1‐40 (Kd=4.4 nm) and amylin (Kd=4.5 nm), implicated, respectively in Alzheimer's disease and diabetes. The Scatchard analysis of surface plasmon resonance data obtained for a series of amphiphilic, PiB derivative GdL complexes indicate that their Aβ1‐40 or amylin binding affinity varies with their concentration, thus micellar aggregation state. The GdL chelates also affect peptide aggregation kinetics, as probed by thioflavin‐T fluorescence assays. A 2D NMR study allowed identifying that the hydrophilic region of Aβ1‐40 is involved in the interaction between the monomer peptide and the Gd3+ complex. Finally, ex vivo biodistribution experiments were conducted in healthy mice by using 111In labeled analogues. Their pancreatic uptake, ∼3 %ID g−1, is promising to envisage amylin imaging in diabetic animals. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that leads to cartilage damage, joint destruction and bone erosions. Serological analysis is one of the most important tools for diagnosis of RA. The aims of studies were the synthesis of an amino-acid library of epitope CHHLDKSIKEDVQFADSRI corresponding to the flap region of H. pylori urease and investigation recognition by serum antibodies from one rheumatoid arthritis patient (RAP) and one volunteer blood donor (VBD) tested by two semi-quantitative methods. In this study we compared two immunoblot variants for estimation of antibodies recognizing five synthetic peptides corresponding to the urease flap region sequence from different organisms. One immunoblot variant was a classic dot-blot using HRP-conjugated anti-human antibodies, where the level of bound immunoglobulins was estimated by digitization of color formed by reaction with secondary antibody. The second immunoblot variant was based on fluorescein-conjugated anti human antibodies. Both semi-quantitative methods were effective for evaluation of antibodies, and their advantages and disadvantages are discussed. To identify the amino-acid residues critical for reaction with antibodies, an amino-acid scan of the complete sequence of the flap region from Helicobacter pylori urease (epitope BK-61B) was conducted. Each sub-library (1–19) contained 19 peptides, each with different amino acids (a–w) at defined positions. All components of the library were synthesized using a divergent strategy. Patterns of serological reaction with the peptide library were unique for each serum sample from an RA patient or control blood donor. The amino-acid residues in epitope BK-61B necessary for strong reaction with antibodies and preventing reaction with antibodies were identified. [ABSTRACT FROM AUTHOR]

A collection of N-triazinylammonium sulfonates, designed according to the concept of 'superactive esters', was obtained by treatment of ammonium sulfonates with 2-chloro-4,6-dimethoxy-1,3,5-triazine. The structure of the tertiary amine as well as sulfonate anion influenced their reactivity and stability in N, N-dimethylformamide (DMF) solution. The reagents were successfully used in solution- and solid-phase synthesis of Z-, Boc-, and Fmoc-protected peptides containing natural and unnatural sterically hindered amino acids as well as in [2+1] fragment condensation approaches, yielding the final products in 80-100 % yield and high optical purity. In manual SPPS of the [Aib]2[Aib]4-enkephalin analogue and the ACP(65-74) peptide fragment VQAAIDYINEG, several sulfonates yielded peptides significantly faster than TBTU or HATU. Comparative analyses demonstrated that 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium 4-toluenesulfonate was the most versatile reagent in a wide range of coupling procedures. [ABSTRACT FROM AUTHOR]

Front Cover: Concentration-Dependent Interactions of Amphiphilic PiB Derivative Metal Complexes with Amyloid Peptides A and Amylin (Chem. Eur. J. 6/2021) Keywords: amylin; amyloid peptide; A ; metal complex; micellar aggregation EN amylin amyloid peptide A metal complex micellar aggregation 1860 1860 1 01/29/21 20210126 NES 210126 B Metal chelates targeted to amyloid peptides b are widely explored as diagnostic tools or therapeutic agents. Amylin, amyloid peptide, A , metal complex, micellar aggregation. [Extracted from the article]

Invited for the cover of this issue are Jean-François Morfin and Éva Tóth at the CNRS in Orléans, and their collaborators from University of Debrecen, University of Coimbra and Université de Toulouse. The image depicts that when an amphiphilic compound is intravenously injected, monomer, pre-micellar and micellar forms can co-exist in the blood and have different affinities for amyloid peptides. Read the full text of the article at 10.1002/chem.202004000., (© 2021 Wiley-VCH GmbH.)

Overlapping decapeptide fragments of H. pylori urease subunit A (UreA) were synthesized and tested with polyclonal antibodies against Canavalia ensiformis (Jack bean) urease. The linear epitopes of UreA identified using the dot blot method were then examined using epitope mapping. For this purpose, series of overlapping fragments of UreA, frameshifted ± four amino acid residues were synthesized. Most of the UreA epitopes which reacted with the Jack bean urease polyclonal antibodies had been recognized in previous studies by monoclonal antibodies against H. pylori urease. Fragments 11 - 24, 21 - 33, and 31 - 42 were able to interact with the Jack bean urease antibodies, giving stable immunological complexes. However, the lack of recognition by these antibodies of all the components in the peptide map strongly suggests that a non-continuous (nonlinear) epitope is located on the N-terminal domain of UreA., (© 2018 Wiley-VHCA AG, Zurich, Switzerland.)