5440-55-1Relevant articles and documents
Potent immunosuppressants, 2-alkyl-2-aminopropane-1,3-diols
Fujita, Tetsuro,Hirose, Ryoji,Yoneta, Masahiko,Sasaki, Shigeo,Inoue, Kenichiro,Kiuchi, Masatoshi,Hirase, Susumu,Chiba, Kenji,Sakamoto, Hiroshi,Arita, Masafumi
, p. 4451 - 4459 (1996)
Several immunosuppressants, ISP-I [(2S,3R,4R)-(E)-2-amino-3,4-dihydroxy- 2-(hydroxymethyl)-14-oxoeicos-6-enoic acid, myriocin = thermozymocidin] and mycestericins A-G, were isolated from culture broths of Isaria sinclairii and Mycelia sterilia, respectively. In order to investigate structure-activity relationships, extensive modifications of ISP-I were conducted, and it was established that the fundamental structure possessing the immunosuppressive activity is a symmetrical 2-alkyl-2-aminopropane-1,3-diol. The tetradecyl, pentadecyl, and hexadecyl derivatives prolonged rat skin allograft survival in the combination of LEW donor and F344 recipient and were more effective than cyclosporin A. Among them, 2-amino-2-tetradecylpropane-1,3-diol hydrochloride, ISP-I-55, showed the lowest toxicity. ISP-I-55 is a promising lead compound for the development of effective immunosuppressants for organ transplantations and for the treatment of autoimmune diseases.
Erratum: Pro-apoptotic activity of lipidic α-amino acids isolated from Protopalythoa variabilis (Bioorg. Med. Chem. (2010) 18 (7997-8004))
Wilke, Diego Veras,Jimenez, Paula Christine,Araújo, Renata Mendona,Da Silva, Wildson Max Barbosa,Pessoa, Otília Deusdênia Loiola,Silveira, Edilberto Rocha,Pessoa, Claudia,De Moraes, Manoel Odorico,Skwarczynski, Mariusz,Simerska, Pavla,Toth, Istvan,Costa-Lotufo, Letícia Veras
, p. 1366 - 1366 (2011)
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Design of bioavailable derivatives of 12-(3-adamantan-1-yl-ureido)dodecanoic acid, a potent inhibitor of the soluble epoxide hydrolase
Kim, In-Hae,Nishi, Kosuke,Tsai, Hsing-Ju,Bradford, Tanya,Koda, Yasuko,Watanabe, Takaho,Morisseau, Christophe,Blanchfield, Joanne,Toth, Istvan,Hammock, Bruce D.
, p. 312 - 323 (2008/02/04)
The soluble epoxide hydrolase (sEH) plays an important role in the metabolism of endogenous chemical mediators involved in blood pressure regulation and vascular inflammation. 12-(3-Adamantan-1-yl-ureido)-dodecanoic acid (AUDA, 1) is a very active inhibit
97. Synthesis of Unnatural Lipophilic N-(9H-Fluoren-9-ylmethoxy)carbonyl-Substituted α-Amino Acids and Their Incorporation into Cyclic RGD-Peptides: A Structure-Activity Study
Koppitz, Marcus,Huenges, Martin,Gratias, Rainer,Kessler, Horst,Goodman, Simon L.,Jonczyk, Alfred
, p. 1280 - 1300 (2007/10/03)
The ανβ3 integrin is implicated in human tumor metastasis and angiogenesis. It has been shown that structures of the sequence cyclo(-Arg1-Gly2-Asp3-D-Phe 4-Xaa5-) (I) and cyclo(-Arg1-Gly2-Asp3-Phe 4-D-Xaa5-) (II) bind with high affinity and the latter with high selectivity to this receptor. The residues Xaa and D-Xaa accept a broad variety of amino acids. Here, we report on the synthesis, activities, and conformational analysis of cyclic Arg-Gly-Asp (RGD) peptides containing lipophilic amino acids Xaa or D-Xaa in position 5. For I, these were (2S)-2-aminohexadecanoic acid (Ahd) and N-hexadecylglycine (Hd-Gly) and in II, D-Ahd and Hd-Gly, and, for control purposes, Ahd were incorporated (Fig. 1). The enantiomerically pure α-amino acids were obtained by non-enantioselective synthesis and subsequent enzymatic separation of isomers using acylase I (Scheme). Hd-Gly was prepared in a modified procedure according to Stewart from ethyl bromoacetate and hexadecylamine (Scheme). The synthesis and physicochemical properties of the corresponding (9H-fluoren-9-ylmethoxy)carbonyl (Fmoc) derivatives, compatible with solid-phase peptide synthesis, are described. Structure elucidation by NMR reveals that the lipid modification has no significant impact on the template structures when incorporated into them. For peptides I with Xaa = Ahd or Hd-Gly (1 or 2), a βII′/γ-turn-like arrangement with D-Phe in i + 1 position of the β-turn is found. Peptides II with D-Xaa = D-Ahd or Hd-Gly (3 or 4) exhibit a βII′/γ-turn conformation with Gly in i + 1 position of the β-turn, whereas II with Ahd instead of D-Xaa, i.e., lacking a D-amino acid in position 4 or 5 (5), adopts no defined conformation. However, in assays of receptor specificity employing human ανβ3 integrin, the compounds exhibit IC50 values ranging from nanomolar to less than millimolar. These results indicate that although the arrangement of the pharmacophoric groups is preserved in the target compounds, the biological activity is highly dependent on spatial requirements of the lipid anchor in the receptor binding pocket. Obviously, only certain positions do not affect the binding.
