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Publications

Vasco, A. V.; Moya, C. G.; Gröger, S.; Brandt, W.; Balbach, J.; Pérez, C. S.; Wessjohann, L. A.; Rivera, D. G.; Insights into the secondary structures of lactam N-substituted stapled peptides Org. Biomol. Chem. 18 3838-3842 (2020) DOI: 10.1039/D0OB00767F
  • Abstract
  • BibText
  • RIS

Stapled peptides derived from the Ugi macrocyclization comprise a special class of cyclopeptides with an N-substituted lactam bridge cross-linking two amino acid side chains. Herein we report a comprehensive analysis of the structural factors influencing the secondary structure of these cyclic peptides in solution. Novel insights into the s-cis/s-trans isomerism and the effect of N-functionalization on the conformation are revealed.

Publications

Vattekkatte, A.; Garms, S.; Brandt, W.; Boland, W.; Enhanced structural diversity in terpenoid biosynthesis: enzymes, substrates and cofactors Org. Biomol. Chem. 16 348-362 (2018) DOI: 10.1039/C7OB02040F
  • Abstract
  • BibText
  • RIS

The enormous diversity of terpenes found in nature is generated by enzymes known as terpene synthases, or cyclases. Some are also known for their ability to convert a single substrate into multiple products. This review comprises monoterpene and sesquiterpene synthases that are multiproduct in nature along with the regulation factors that can alter the product specificity of multiproduct terpene synthases without genetic mutations. Variations in specific assay conditions with focus on shifts in product specificity based on change in metal cofactors, assay pH and substrate geometry are described. Alterations in these simple cellular conditions provide the organism with enhanced chemodiversity without investing into new enzymatic architecture. This versatility to modulate product diversity grants organisms, especially immobile ones like plants with access to an enhanced defensive repertoire by simply altering cofactors, pH level and substrate geometry.

Publications

Morejon, M. C.; Laub, A.; Kaluđerović, G. N.; Puentes, A. R.; Hmedat, A. N.; Otero-González, A. J.; Rivera, D. G.; Wessjohann, L. A.; A multicomponent macrocyclization strategy to natural product-like cyclic lipopeptides: synthesis and anticancer evaluation of surfactin and mycosubtilin analogues Org. Biomol. Chem. 15 3628-3637 (2017) DOI: 10.1039/C7OB00459A
  • Abstract
  • BibText
  • RIS

A multicomponent macrocyclization strategy towards cyclic lipopeptides is described. The approach relies on the utilization of the Ugi and Passerini multicomponent reactions for the cyclization of peptides and oxo-peptides, and here it is employed for the construction of a small library of analogues of the natural products mycosubtilin and surfactin A. A key feature of this method is the simultaneous incorporation of either one or two exocyclic lipid tails along with the macrocyclic ring closure, which is only possible due to the multicomponent nature of the macrocyclization step. The evaluation of the anticancer activity of the lipopeptide library showed that the installation of a second lipid moiety in the surfactin scaffold leads to a more potent cytotoxicity in cancer cells. This is a new example of the multicomponent reaction potential in rapidly producing natural product analogues for biological screening.

Publications

Sultani, H. N.; Haeri, H. H.; Hinderberger, D.; Westermann, B.; Spin-labelled diketopiperazines and peptide–peptoid chimera by Ugi-multi-component-reactions Org. Biomol. Chem. 14 11336-11341 (2016) DOI: 10.1039/C6OB02194H
  • Abstract
  • BibText
  • RIS

For the first time, spin-labelled coumpounds have been obtained by isonitrile-based multi component reactions (IMCRs). The typical IMCR Ugi-protocols offer a simple experimental setup allowing structural variety by which labelled diketopiperazines (DKPs) and peptide–peptoid chimera have been synthesized. The reaction keeps the paramagnetic spin label intact and offers a simple and versatile route to a large variety of new and chemically diverse spin labels.

Publications

Vattekkatte, A.; Gatto, N.; Schulze, E.; Brandt, W.; Boland, W.; Inhibition of a multiproduct terpene synthase from Medicago truncatula by 3-bromoprenyl diphosphates Org. Biomol. Chem. 13 4776-4784 (2015) DOI: 10.1039/c5ob00506j
  • Abstract
  • BibText
  • RIS

The multiproduct sesquiterpene synthase MtTPS5 from Medicago truncatula catalyzes the conversion of farnesyl diphosphate (FDP) into a complex mixture of 27 terpenoids. 3-Bromo substrate analogues of geranyl diphosphate (3-BrGDP) and farnesyl diphosphate (3-BrFDP) were evaluated as substrates of MTPS5 enzyme. Kinetic studies demonstrated that these compounds were highly potent competitive inhibitors of the MtTPS5 enzyme with fast binding and slow reversibility. Since there is a lack of knowledge about the crystal structure of multiproduct terpene synthases, these molecules might be ideal candidates for obtaining a co-crystal structure with multiproduct terpene synthases. Due to the structural and mechanistic similarity between various terpene synthases we expect these 3-bromo isoprenoids to be ideal probes for crystal structure studies.

Publications

Ricardo, M. G.; Morales, F. E.; Garay, H.; Reyes, O.; Vasilev, D.; Wessjohann, L. A.; Rivera, D. G.; Bidirectional macrocyclization of peptides by double multicomponent reactions Org. Biomol. Chem. 13 438-446 (2015) DOI: 10.1039/c4ob01915f
  • Abstract
  • BibText
  • RIS

Increasing the diversity of peptide cyclization methods is an effective way of accessing new types of macrocyclic chemotypes featuring a wide variety of ring sizes and topologies. Multicomponent reactions (MCRs) are processes capable of generating great levels of molecular diversity and complexity at low synthetic cost. In an attempt to further exploit MCRs in the field of cyclopeptides, we describe a bidirectional multicomponent approach for the synthesis of N-alkylated macrocyclic peptides of varied sequences and cross-linking positions. The process relies on the execution of two Ugi reactions between peptide diacids and diisocyanides. Varying the amino component enabled the installation of exocyclic elements of diversity, while skeletal diversity was created through different side chain and backbone cyclizations. This procedure shows prospects for the rapid scanning of the chemical space of macrocyclic peptides for applications in chemical biology and drug discovery.

Publications

Thuy, T. T.; Anh, N. T. H.; Sung, T. V.; Dan, T. K.; Chinh, N. B.; Quang, N.; Franke, K.; Arnold, N.; Wessjohann, L.; Phytochemical study on the plants of the antidrug medication heantos 4: Part 4. Phthalides, fatty acids, oligosaccharide esters and miscellaneous compounds Vietnam J. Chem. 51 546-550 (2013)
  • BibText
  • RIS

0

Publications

Thuy, T. T.; Anh, N. H.; Sung, T. V.; Dan, T. K.; Chinh, N. B.; Quang, N.; Franke, K.; Arnold, N.; Wessjohann, L.; Phytochemical study on the plants of the antidrug medication heantos 4: Part 1. Alkaloids and other nitrogen containing compounds Vietnam J. Chem. 51 185-189 (2013)
  • BibText
  • RIS

0

Publications

Anh, N. T. H.; Thuy, T. T.; Sung, T. V.; Dan, T. K.; Chinh, N. B.; Quang, N.; Franke, K.; Arnold, N.; Wessjohann, L.; Phytochemical study on the plants of the antidrug medication heantos 4: Part 3. Homoisoflavonoid, flavonoid and phenolic compounds Vietnam J. Chem. 51 358-362 (2013)
  • BibText
  • RIS

0

Publications

Anh, N. T. H.; Thuy, T. T.; Sung, T. V.; Dan, T. K.; Chinh, N. B.; Quang, N.; Franke, K.; Arnold, N.; Wessjohann, L.; Phytochemical study on the plants of the antidrug medication heantos 4: Part 2. Terpenoid- and steroid compounds Vietnam J. Chem. 51 190-194 (2013)
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