scholarly journals The role of chemical synthesis in developing RiPP antibiotics

2021 ◽  
Vol 50 (7) ◽  
pp. 4245-4258
Author(s):  
Sam M. Rowe ◽  
David R. Spring
Keyword(s):  
Chemical Synthesis ◽  
Lasso Peptides ◽  
Modified Peptides

This tutorial review discusses the potential of ribosomally synthesised and post-translationally modified peptides (RiPPs) as antimicrobials and looks at the chemical synthesis of three classes of RiPP: lasso peptides, cyclotides, and lanthipeptides.

scholarly journals The Importance of 6-Aminohexanoic Acid as a Hydrophobic, Flexible Structural Element

2021 ◽  
Vol 22 (22) ◽  
pp. 12122
Author(s):  
Agnieszka Markowska ◽  
Adam Roman Markowski ◽  
Iwona Jarocka-Karpowicz
Keyword(s):  
Amino Acid ◽  
Chemical Synthesis ◽  
Biologically Active ◽  
Flexible Structure ◽  
Amino Group ◽  
Structural Element ◽  
Synthetic Fibers ◽  
Active Structures ◽  
Modified Peptides

6-aminohexanoic acid is an ω-amino acid with a hydrophobic, flexible structure. Although the ω-amino acid in question is mainly used clinically as an antifibrinolytic drug, other applications are also interesting and important. This synthetic lysine derivative, without an α-amino group, plays a significant role in chemical synthesis of modified peptides and in the polyamide synthetic fibers (nylon) industry. It is also often used as a linker in various biologically active structures. This review concentrates on the role of 6-aminohexanoic acid in the structure of various molecules.

scholarly journals Peptides Bearing Multiple Post-Translational Modifications as Antigenic Targets for Severe Rheumatoid Arthritis Patients

2021 ◽  
Vol 22 (24) ◽  
pp. 13290
Author(s):  
Cristina García-Moreno ◽  
María J. Gómara ◽  
Raúl Castellanos-Moreira ◽  
Raimon Sanmartí ◽  
Isabel Haro
Keyword(s):  
Rheumatoid Arthritis ◽  
Structural Damage ◽  
Serum Antibody ◽  
Joint Damage ◽  
Erosive Disease ◽  
Post Translational Modifications ◽  
Diagnosis And Prognosis ◽  
Modified Peptides ◽  
Chimeric Peptides

Rheumatoid arthritis (RA) is characterized by the presence of autoantibodies that are of paramount importance for the diagnosis and prognosis of the disease and have been implicated in its pathogenesis. Proteins resulting from post-translational modifications (PTMs) are capable of triggering autoimmune responses important for the development of RA. In this work, we investigate serum antibody reactivity in patients with an established RA against a panel of chimeric peptides derived from fibrin and filaggrin proteins and bearing from one to three PTMs (citrullination, carbamylation and acetylation) by home-designed ELISA tests (anti-AMPA autoantibodies). The role of anti-AMPAs as biomarkers linked to the presence of a more severe RA phenotype (erosive disease with radiological structural damage) and to the presence of interstitial lung disease (ILD), a severe extra-articular manifestation in RA patients entailing a high mortality, was also analyzed. In general, the association with the clinical phenotype of RA was confirmed with the different autoantibodies, and especially for IgA and IgM isotypes. The prevalence of severe joint damage was only statistically significant for the IgG isotype when working with the peptide bearing three PTMs. Furthermore, the median titers were significantly higher in patients with RA-ILD, a finding not observed for the IgG isotype when working with the single- and double-modified peptides.

scholarly journals Put a Bow on It: Knotted Antibiotics Take Center Stage

Antibiotics ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 117 ◽  
Author(s):  
Stephanie Tan ◽  
Gaelen Moore ◽  
Justin Nodwell
Keyword(s):  
Current Knowledge ◽  
Chemical Diversity ◽  
Peptide Antibiotics ◽  
Linear Peptide ◽  
Peptidoglycan Biosynthesis ◽  
Lasso Peptides ◽  
Lipid Ii ◽  
Modified Peptides ◽  
Domains Of Life ◽  
Peptide Biosynthesis

Ribosomally-synthesized and post-translationally modified peptides (RiPPs) are a large class of natural products produced across all domains of life. The lasso peptides, a subclass of RiPPs with a lasso-like structure, are structurally and functionally unique compared to other known peptide antibiotics in that the linear peptide is literally “tied in a knot” during its post-translational maturation. This underexplored class of peptides brings chemical diversity and unique modes of action to the antibiotic space. To date, eight different lasso peptides have been shown to target three known molecular machines: RNA polymerase, the lipid II precursor in peptidoglycan biosynthesis, and the ClpC1 subunit of the Clp protease involved in protein homeostasis. Here, we discuss the current knowledge on lasso peptide biosynthesis as well as their antibiotic activity, molecular targets, and mechanisms of action.

Role of the solvent medium in the wet-chemical synthesis of CuSbS2, Cu3SbS3, and bismuth substituted Cu3SbS3

2020 ◽  
Vol 132 (1) ◽  
Author(s):  
Shalu Atri ◽  
Meenakshi Gusain ◽  
Prashant Kumar ◽  
Sitharaman Uma ◽  
Rajamani Nagarajan
Keyword(s):  
Chemical Synthesis ◽  
Solvent Medium ◽  
Wet Chemical Synthesis ◽  
Wet Chemical

scholarly journals The Role of Proteins in Biosilicification

Scientifica ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-22 ◽  
Author(s):  
Daniel Otzen
Keyword(s):  
Self Assembly ◽  
Organic Matrix ◽  
Specific Protein ◽  
Colloidal Systems ◽  
Protein Properties ◽  
Modified Peptides ◽  
Fundamental Biology ◽  
Living Organisms ◽  
Insight Into

Although the use of silicon dioxide (silica) as a constituent of living organisms is mainly restricted to diatoms and sponges, the ways in which this process is controlled by nature continue to inspire and fascinate. Both diatoms and sponges carry out biosilificiation using an organic matrix but they adopt very different strategies. Diatoms use small and heavily modified peptides called silaffins, where the most characteristic feature is a modulation of charge by attaching long chain polyamines (LCPAs) to lysine groups. Free LCPAs can also cooperate with silaffins. Sponges use the enzyme silicatein which is homologous to the cysteine protease cathepsin. Both classes of proteins form higher-order structures which act both as structural templates and mechanistic catalysts for the polycondensation reaction. In both cases, additional proteins are continuously being discovered which modulate the process further. This paper concentrates on the role of these proteins in the biosilification process as well as in various applications, highlighting areas where focus on specific protein properties may provide further insight. The field of biosilification is a crossroads of different disciplines, where insight into the energetics and mechanisms of molecular self-assembly combine with fundamental biology, complex multicomponent colloidal systems, and an impressive array of potential technological applications.

scholarly journals Chemical synthesis of erythropoietin glycoforms for insights into the relationship between glycosylation pattern and bioactivity

2016 ◽  
Vol 2 (1) ◽  
pp. e1500678 ◽  
Author(s):  
Masumi Murakami ◽  
Tatsuto Kiuchi ◽  
Mika Nishihara ◽  
Katsunari Tezuka ◽  
Ryo Okamoto ◽  
...  
Keyword(s):  
Biological Activity ◽  
Chemical Synthesis ◽  
Glycosylation Pattern ◽  
Chemical Ligation ◽  
Homogeneous Form ◽  
Synthetic Strategy ◽  
Coupling Strategy ◽  
The Relationship

The role of sialyloligosaccharides on the surface of secreted glycoproteins is still unclear because of the difficulty in the preparation of sialylglycoproteins in a homogeneous form. We selected erythropoietin (EPO) as a target molecule and designed an efficient synthetic strategy for the chemical synthesis of a homogeneous form of five EPO glycoforms varying in glycosylation position and the number of human-type biantennary sialyloligosaccharides. A segment coupling strategy performed by native chemical ligation using six peptide segments including glycopeptides yielded homogeneous EPO glycopeptides, and folding experiments of these glycopeptides afforded the correctly folded EPO glycoforms. In an in vivo erythropoiesis assay in mice, all of the EPO glycoforms displayed biological activity, in particular the EPO bearing three sialyloligosaccharides, which exhibited the highest activity. Furthermore, we observed that the hydrophilicity and biological activity of the EPO glycoforms varied depending on the glycosylation pattern. This knowledge will pave the way for the development of homogeneous biologics by chemical synthesis.

General rules of fragmentation evidencing lasso structures in CID and ETD

The Analyst ◽  
2018 ◽  
Vol 143 (5) ◽  
pp. 1157-1170 ◽  
Author(s):  
K. Jeanne Dit Fouque ◽  
H. Lavanant ◽  
S. Zirah ◽  
J. D. Hegemann ◽  
C. D. Fage ◽  
...  
Keyword(s):  
Lasso Peptides ◽  
General Rules ◽  
Modified Peptides

Lasso peptides are ribosomally synthesized and post-translationally modified peptides (RiPPs) characterized by a mechanically interlocked structure in which the C-terminal tail of the peptide is threaded and trapped within an N-terminal macrolactam ring.

Aryltetralin-type lignan of Podophyllum: a comprehensive review

2021 ◽  
Vol 11 ◽  
Author(s):  
Dharmendra Kumar ◽  
Mogana Rajagopal ◽  
Gabriel Akyirem Akowuah ◽  
Yong-Xin Lee ◽  
Chua Wei Chong ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Chemical Synthesis ◽  
Chemical Modification ◽  
Broad Spectrum ◽  
Anticancer Agent ◽  
Review Article ◽  
Pharmacological Activities ◽  
Comprehensive Review ◽  
Podophyllotoxin Derivatives

: Podophyllotoxin is a nonalkaloidtoxin aryltetralin lactone lignan, occurring naturally and extracted from the rhizomes and roots of Podophyllum species. Podophyllotoxin and its derivatives have shown to possess a broad spectrum of pharmacological activities, mainly antineoplastic and antiviral properties. Podophyllotoxin is served as a potential anticancer agent and also the precursor for the chemical synthesis of some clinically important anticancer agents.The chemical modification and pharmacological investigation of podophyllotoxin derivatives have become a concern nowadays. Research interest has been stimulated in the innovation of podophyllotoxin derivatives as the semi-synthetic anticancer agent, especially etoposide and teniposide. Podophyllotoxin and its derivatives are available in several formulations and also found to be effective in combination therapy. This review article aims to provide an overview of the role of podophyllotoxin, its mechanism of action, pharmacological activities, pharmacokinetics, available formulations, and its effects in combination therapy. This article also reviewed the biosynthesis, structure and modifications of podophyllotoxin and its derivatives as an anticancer agent.

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