- Short self-assembling peptides with a urea bond: A new type of supramolecular peptide hydrogel materials
-
There is an increasing need to develop short self-assembling peptides (SAPs) that can form hydrogels for cell engineering and biomedical applications. In this study, we proposed new short self-assembling peptides with a symmetric structure via a urea bond
- Tsutsumi, Hiroshi,Tanaka, Kunifumi,Chia, Jyh Yea,Mihara, Hisakazu
-
-
- Total synthesis of pentosidine
-
Pentosidine, a biologically important advanced glycation endproduct, has been accessed in a rapid, high-yielding manner. The synthesis was accomplished via a six-step sequence starting with 3-amino-2-chloropyridine and features a palladium-catalyzed tande
- Rosenberg, Adam J.,Clark, Daniel A.
-
supporting information
p. 4678 - 4681
(2012/10/29)
-
- Design, synthesis, and biological testing of potential heme-coordinating nitric oxide synthase inhibitors
-
Based on computer modeling of the active site of nitric oxide synthases (NOS), a series of 10 amidine compounds (9-18) was designed including potential inhibitors that involve the coordination of side-chain functional groups with the iron of the heme cofactor. The most potent and selective compound was the methylthio amidine analogue 9, which was more potent than l-nitroarginine with 185-fold selectivity for inhibition of neuronal NOS over endothelial NOS. It also exhibited time-dependent inhibition, but did not involve the mechanism previously proposed for other amidine inhibitors of NOS. None of the compounds, however, exhibited heme-binding characteristics according to absorption spectroscopy.
- Litzinger, Elizabeth A.,Martasek, Pavel,Roman, Linda J.,Silverman, Richard B.
-
p. 3185 - 3198
(2007/10/03)
-
- Synthesis and precursor-directed biosynthesis of new hormaomycin analogues
-
Several new analogues of hormaomycin (1), a peptide lactone with interesting biological activities, were prepared by total synthesis or by precursor-directed biosynthesis. The new analogues 2a-c, 3a-c, O-MOM-1 and epi-O-MOM-1 as well as the model acyl tri
- Zlatopolskiy, Boris D.,Radzom, Markus,Zeeck, Axel,De Meijere, Armin
-
p. 1525 - 1534
(2007/10/03)
-
- An expeditious synthesis of pentosidine, an advanced glycation end product
-
The chemical synthesis of pentosidine (1), an advanced glycation end product, was achieved via the asymmetric alkylation of the chiral schiff base derived from (+)-2-hydroxy-3-pinanone ((+)-HyPN) and glycine tert-butyl ester, the mercury salt mediated intramolecular guanylation, and the regioselective alkylation of imidazo[4,5-b]pyridine ring. This reliable synthetic achievement will promise availability of pentosidine (1) in quantities.
- Yokokawa, Fumiaki,Sugiyama, Hideyuki,Shioiri, Takayuki,Katagiri, Noriko,Oda, Osamu,Ogawa, Hiroshi
-
p. 4759 - 4766
(2007/10/03)
-
- Efficient total synthesis of pentosidine, an advanced glycation endproduct
-
The efficient total synthesis of pentosidine (1), an advanced glycation endproduct, was achieved using the asymmetric alkylation of a chiral schiff base (2), the intramolecular guanylation with mercury (II) chloride, and the quaternization accompanied by removal of the trityl group as key steps.
- Sugiyama, Hideyuki,Yokokawa, Fumiaki,Shioiri, Takayuki,Katagiri, Noriko,Oda, Osamu,Ogawa, Hiroshi
-
p. 2569 - 2572
(2007/10/03)
-
- Heterocyclic analogues of L-citrulline as inhibitors of the isoforms of nitric oxide synthase (NOS) and identification of N(δ)-(4,5-dihydrothiazol-2-yl)ornithine as a potent inhibitor
-
L-Thiocitrulline is a known potent inhibitor of several isoforms of nitric oxide synthase (NOS). To explore the structure-activity relationships (SARs) for this molecule in more depth than has previously been reported, three analogues substituted at the sulphur of the isothioureas have been synthesised. In two of these, the S-substituent was 'tied back' sterically by cyclisation to the nitrogen remote from the amino-acid unit. N(δ)-(4,5-Dihydrothiazol-2-yl)ornithine was identified as an inhibitor of rat inducible and constitutive isoforms of NOS and of a constitutive NOS derived from a human tumour xenograft. Analogous N(δ)-(thiazol-2-yl)ornithines were less active, whereas the corresponding N(δ)-(oxazol-2-yl)ornithine and N(δ)-(pyrimidin-2-yl)ornithine failed completely to inhibit NOS. A new efficient preparation of the critical synthetic intermediate, N(α)-Boc-thiocitrulline t-butyl ester, has been developed. Further exploration of the SAR with 2-amino-5-(heterocyclylthio)pentanoic acids (synthesised from 2-(Boc-amino)-5-bromopentanoic acid t-butyl ester), with N-(4-aminobutyl)thiourea and with 2-(4-aminobutylamino)-4,5-dihydrothiazole enabled refinement of our previous model for binding of the substrate, L-arginine, and the inhibitors to NOS.
- Ulhaq, Saraj,Chinje, Edwin C.,Naylor, Matthew A.,Jaffar, Mohammed,Stratford, Ian J.,Threadgill, Michael D.
-
p. 1787 - 1796
(2007/10/03)
-
- α-Functionalized phosphonylphosphinates: Synthesis and evaluation as transcarbamoylase inhibitors
-
Diverse α-methyl-substituted phosphonylphosphinates (P-C-P-C-X) are accessible from a protected, pentafluorophenylsulfonated phosphonylphosphinate via nucleophilic displacement. The utility of this route is demonstrated with several nitrogen nucleophiles. The resulting amine and amino acid phosphonylphosphinate derivatives were evaluated as inhibitors of Streptococcus faecalis ornithine transcarbamoylase (OTC). Compared with the structurally related phosphonoacetyl-L-ornithine (L-PALO), a known inhibitor of OTCs from various sources, the phosphonylphosphinates are surprisingly poor inhibitors, binding several orders of magnitude less tightly to the enzyme. These results suggest that the tetrahedral intermediate formed in the normal transcarbamoylase reaction is poorly mimicked by a tetrahedral and anionic phosphonate, either because of directly unfavorable interactions with a hydrogen-bond acceptor within the active site or because transition-state analogues are unable to induce the protein conformation changes that normally accompany reaction.
- Flohr, Alexander,Aemissegger, Andreas,Hilvert, Donald
-
p. 2633 - 2640
(2007/10/03)
-
- Synthesis and Biological Activity of the Novel Nitric Oxide Synthase Inhibitor Nω'-Hydroxy-Nω-methyl-L-arginine
-
Nω'-Hydroxy-Nω-methyl-L-arginine has been sythesised in eight steps from N5-(benzyloxycarbonyl)-L-ornithine and has been found to inhibit the biosynthesis of nitric oxide.
- Moynihan, Humphrey A.,Roberts, Stanley M.,Weldon, Hazel,Allcock, Graham H.,Aenggard, Erik E.,Warner, Timothy D.
-
p. 769 - 772
(2007/10/02)
-
- Synthesis of 15N omega-hydroxy-L-arginine and ESR and 15N-NMR studies for the elucidation of the molecular mechanism of enzymic nitric oxide formation from L-arginine.
-
N omega-Hydroxy-L-arginine (2) was prepared by a multi-stage synthesis; the key step was the addition of hydroxylamine to the protected cyanamide 8. The presence of N-hydroxyguanidines was confirmed, above all, by 15N-NMR investigations. 15N omega-Hydroxy
- Clement,Schnoerwangen,Kaempchen,Mordvintcev,Muelsch
-
p. 793 - 798
(2007/10/02)
-