AI Article Synopsis
Article Abstract
Four new microcystin congeners are described including the first three examples of microcystins containing the rare doubly homologated tyrosine residue 2-amino-5-(4-hydroxyphenyl)pentanoic acid (Ahppa) (1-4). Large-scale harvesting and biomass processing allowed the isolation of substantial quantities of these compounds, thus enabling complete structure determination by NMR as well as cytotoxicity evaluation against selected cancer cell lines. The new Ahppa-toxins all incorporate Ahppa residues at the 2-position, and one of these also has a second Ahppa at position 4. The two most lipophilic Ahppa-containing microcystins showed 10-fold greater cytotoxic potency against human tumor cell lines (A549 and HCT-116) compared to microcystin-LR (5). The presence of an Ahppa residue in microcystin congeners is difficult to ascertain by MS methods alone, due to the lack of characteristic fragment ions derived from the doubly homologated side chain. Owing to their unexpected cytotoxic potency, the potential impact of the compounds on human health should be further evaluated.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/acs.jnatprod.7b00986 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Doubly Homologated Tyrosine-Containing Peptides from the Cyanobacterium NIES-4285 and Their Biosynthesis.
J Nat Prod
November 2024
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
Chemical investigation of the cyanobacterium NIES-4285 led to the isolation of six new natural products, microginins 705 (), 719 (), 733A (), 733B (), and 733C (), and anabaenopeptin 885 (), and three known compounds, anabaenopeptins 871 (), B (), and F (). Planar structures and absolute configurations for - were determined by 2D NMR, HRMS, and Marfey's analyses. Microginin 733C (), and anabaenopeptins 871 () and 885 () contained a unique residue of 2-amino-5-(4-hydroxyphenyl)pentanoic acid (Ahppa): doubly homologated tyrosine (di-hTyr).
View Article and Find Full Text PDFMicrocystins Containing Doubly Homologated Tyrosine Residues from a Microcystis aeruginosa Bloom: Structures and Cytotoxicity.
J Nat Prod
June 2018
Biosortia Pharmaceuticals, Hollings Marine Laboratory , 331 Ft. Johnson Road , Charleston , South Carolina 29412 , United States.
Four new microcystin congeners are described including the first three examples of microcystins containing the rare doubly homologated tyrosine residue 2-amino-5-(4-hydroxyphenyl)pentanoic acid (Ahppa) (1-4). Large-scale harvesting and biomass processing allowed the isolation of substantial quantities of these compounds, thus enabling complete structure determination by NMR as well as cytotoxicity evaluation against selected cancer cell lines. The new Ahppa-toxins all incorporate Ahppa residues at the 2-position, and one of these also has a second Ahppa at position 4.
View Article and Find Full Text PDFStructural Dimorphism of Achiral α,γ-Hybrid Peptide Foldamers: Coexistence of 12- and 15/17-Helices.
Chemistry
March 2017
Department of Chemistry, Indian Institution of Science Education and Research, Dr. Homi Bhabha Road, Pune, 411021, India.
Here, novel 12-helices in α,γ-hybrid peptides composed of achiral α-aminoisobutyric acid (Aib) and 4-aminoisocaproic acid (Aic, doubly homologated Aib) monomers in 1:1 alternation are reported. The 12-helices were indicated by solution and crystal structural analyses of tetra- and heptapeptides. Surprisingly, single crystals of the longer nonapeptide displayed two different helix types: the novel 12-helix and an unprecedented 15/17-helix.
View Article and Find Full Text PDFThe outstanding biological stability of beta- and gamma-peptides toward proteolytic enzymes: an in vitro investigation with fifteen peptidases.
Chembiochem
June 2001
Laboratorium für Organische Chemie der Eidgenössischen Technischen Hochschule, Universitätstrasse 16, 8092 Zürich, Switzerland.
A series of 36 linear and cyclic beta- and gamma-peptides consisting of as few as two, and as many as 15 residues, was offered as substrates to 15 commercially available proteases of bacterial, fungal, and eukaryotic origin, including a beta-lactamase and amidases, as well as most vigorous, nonspecific proteases, such as the 20S proteasome from human erythrocytes. For comparison, an alpha-eicosapeptide and standard substrates of the proteolytic enzymes were included in the investigation. Under conditions of complete cleavage of the alpha-peptide within 15 min the beta- and gamma-peptides were stable for at least 48 h.
View Article and Find Full Text PDFDoubly homologated dihalovinyl and acetylene analogues of adenosine: synthesis, interaction with S-adenosyl-L-homocysteine hydrolase, and antiviral and cytostatic effects.
J Med Chem
March 2000
Department of Chemistry, Florida International University, Miami, Florida 33199, USA.
Treatment of the 6-aldehyde derived by Moffatt oxidation of 3-O-benzoyl-1,2-O-isopropylidene-alpha-D-ribo-hexofuranose (2c) with the dibromo- or bromofluoromethylene Wittig reagents generated in situ with tetrabromomethane or tribromofluoromethane, triphenylphosphine, and zinc gave the dihalomethyleneheptofuranose analogues 3b and 3d, respectively. Acetolysis, coupling with adenine, and deprotection gave 9-(7,7-dibromo-5,6, 7-trideoxy-beta-D-ribo-hept-6-enofuranosyl)adenine (5a) or its bromofluoro analogue 5b. Treatment of 5a with excess butyllithium provided the acetylenic derivative 9-(5,6, 7-trideoxy-beta-D-ribo-hept-6-ynofuranosyl)adenine (6).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!