A Lysyl Oxidase-Responsive Collagen Peptide Illuminates Collagen Remodeling in Wound Healing

Tissue repair and fibrosis involve the dynamic remodeling of collagen, and accurate detection of these sites is of utmost importance. Here, we use a collagen peptide sensor (1) to visualize collagen formation and remodeling during wound healing in mice and humans. We show that the probe binds selectively to sites of collagen formation and remodeling at different stages of healing. Compared to conventional methods, the peptide sensor localizes preferentially to areas of collagen synthesis and remodeling at the wound edge and not in matured fibrillar collagen. We also demonstrate its applicability for in vivo wound imaging and for discerning differential remodeling in wounds of transgenic mice with altered collagen dynamics. Our findings show the value of 1 as a diagnostic tool to rapidly identify the sites of matrix remodeling in tissue sections, which will aid in the conception of new therapeutic strategies for fibrotic disorders and defective tissue repair

Modifying the catalytic activity of lipopeptide assemblies with nucleobases

Biohybrid catalysts that operate in aqueous media are intriguing for systems chemistry. In this paper, we investigate whether control over the self-assembly of biohybrid catalysts can tune their properties. As a model, we use the catalytic activity of functional hybrid molecules consisting of a catalytic H-dPro-Pro-Glu tripeptide, derivatized with fatty acid and nucleobase moieties. This combination of simple biological components merged the catalytic properties of the peptide with the self-assembly of the lipid, and the structural ordering of the nucleobases. The biomolecule hybrids self-assemble in aqueous media into fibrillar assemblies and catalyze the reaction between butanal and nitrostyrene. The interactions between the nucleobases enhanced the order of the supramolecular structures and affected their catalytic activity and stereoselectivity. The results point to the significant control and ordering that nucleobases can provide in the self-assembly of biologically inspired supramolecular catalystsPID2020-119306GB-I00, S2018/NMT-4291 TEC2SPACE, CSIC13-4E-179

Conformational Properties of a Peptidic Catalyst: Insights from NMR Spectroscopic Studies

Peptides have become valuable as catalysts for a variety of different reactions, but little is known about the conformational properties of peptidic catalysts. We investigated the conformation of the peptide H-dPro-Pro-Glu-NH; 2; , a highly reactive and stereoselective catalyst for conjugate addition reactions, and the corresponding enamine intermediate in solution by NMR spectroscopy and computational methods. The combination of nuclear Overhauser effects (NOEs), residual dipolar couplings (RDCs), J-couplings, and temperature coefficients revealed that the tripeptide adopts a single predominant conformation in its ground state. The structure is a type I β-turn, which gains stabilization from three hydrogen bonds that are cooperatively formed between all functional groups (secondary amine, carboxylic acid, amides) within the tripeptide. In contrast, the conformation of the enamine intermediate is significantly more flexible. The conformational ensemble of the enamine is still dominated by the β-turn, but the backbone and the side chain of the glutamic acid residue are more dynamic. The key to the switch between rigidity and flexibility of the peptidic catalyst is the CO; 2; H group in the side chain of the glutamic acid residue, which acts as a lid that can open and close. As a result, the peptidic catalyst is able to adapt to the structural requirements of the intermediates and transition states of the catalytic cycle. These insights might explain the robustness and high reactivity of the peptidic catalyst, which exceeds that of other secondary amine-based organocatalysts. The data suggest that a balance between rigidity and flexibility, which is reminiscent of the dynamic nature of enzymes, is beneficial for peptidic catalysts and other synthetic catalysts

Peptides – Molecular allrounders

The enormous structural and functional diversity available through combining different amino acids into peptides offers numerous exciting opportunities. This article summarizes recent research highlights from my laboratory in the areas of asymmetric catalysis, supramolecular chemistry, and chemical biology. This scope includes the development of bioinspired peptide catalysts, synthetic collagen peptides, supramolecular porous assemblies, and cell-penetrating peptides.ISSN:0009-429

Peptide Receptors – From Selective Molecular Recognition Towards Catalytic Activity

The development of diketopiperazine receptors, a class of two-armed receptors that bind peptides with high selectivity, has been achieved by a combination of on-bead combinatorial binding assays and conformational analysis using X-ray crystal structure analysis and NMR spectroscopy. Furthermore, a general method for the discovery of catalysts within split-and-mix libraries has been developed that is based on the co-immobilization of the potential catalyst and one reactant on the same bead

Peptides as Asymmetric Catalysts for Aldol Reactions

The article summarizes our research devoted to the development of peptidic catalysts for aldol reactions. Using the combinatorial method of 'catalyst–substrate coimmobilization' the peptides H-Pro-Pro-Asp-NH2 and H-Pro-D-Ala-D-Asp-NH2 were identified as highly active and selective catalysts for direct aldol reactions. The results demonstrate that the higher complexity of peptides in comparison to rigid small organocatalysts can be a good trade-off for higher activity

(4R)- and (4S)-Azidoprolines : conformation directing amino acids and sites for functionalization

An ‘azido gauche effect’ determines the conformation of (4S)- and (4R)-azidoproline (Azp) derivatives and affects the s-cis:s-trans conformer ratio of Xaa-Azp bonds. The article summarizes our research on the con- formational analysis of monomers as well as oligomers derived from (4S)Azp and (4R)Azp. We show that (4S)Azp and (4R)Azp can be used to tune the stability of the polyproline II (PPII) helix. In addition we demonstrate that Azp containing oligoprolines are attractive molecular scaffolds with a well-defined helical conformation that can be readily further functionalized using e.g. click chemistry

Organocatalytic Synthesis of Triflones Bearing Two Non-Adjacent Stereogenic Centers

Trifluoromethylsulfones (triflones) are useful compounds for synthesis and beyond. Yet, methods to access chiral triflones are scarce. Here, we present a mild and efficient organocatalytic method for the stereoselective synthesis of chiral triflones using alpha-aryl vinyl triflones, building blocks previously unexplored in asymmetric synthesis. The peptide-catalyzed reaction gives rise to a broad range of gamma-triflylaldehydes with two non-adjacent stereogenic centers in high yields and stereoselectivities. A catalyst-controlled stereoselective protonation following a C-C bond formation is key to control over the absolute and relative configuration. Straightforward derivatization of the products into, e.g., disubstituted delta-sultones, gamma-lactones, and pyrrolidine heterocycles highlights the synthetic versatility of the products.ISSN:1433-7851ISSN:1521-3773ISSN:0570-083

Effect of beta(3)-Amino Acids on the Performance of the Peptidic Catalyst H-dPro-Pro-Glu-NH2

ISSN:0018-019XISSN:1522-267