17702-88-4Relevant articles and documents
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 (1997)
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.
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Haudegond,J.-P. et al.
, p. 3063 - 3065 (1979)
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Sequential reactions from catalytic hydroformylation toward the synthesis of amino compounds
Almeida, Ana R.,Carrilho, Rui M.B.,Peixoto, Andreia F.,Abreu, Artur R.,Silva, Artur,Pereira, Mariette M.
, p. 2389 - 2395 (2017/04/03)
Different families of new amino compounds were efficiently synthesized, through optimized sequential processes, involving rhodium catalyzed hydroformylation as the key step. The selection of appropriate hydroformylation catalytic systems and reaction conditions allowed obtaining aldehydes derived from several n-alkyl olefins, cholest-4-ene and 3-vinyl-1H-indole, which were subsequently transformed, in one-pot, in to α-amino acids via hydroformylation/Strecker reaction, and in to tertiary amines via hydroaminomethylation, with excellent yields.
Synthesis of a library of polycationic lipid core dendrimers and their evaluation in the delivery of an oligonucleotide with hVEGF inhibition
Parekh, Harendra S.,Marano, Robert J.,Rakoczy, Elizabeth P.,Blanchfield, Joanne,Toth, Istvan
, p. 4775 - 4780 (2007/10/03)
This article follows on from our previous work in the area of non-viral gene delivery using polycationic dendrimers (PCDs). Herein we report on the synthesis and efficacy of a new library of lipid core PCDs in the delivery of the anti-angiogenic oligonucleotide (ODN-1) to retinal pigment epithelial cells. ELISA was used to monitor hVEGF levels in cells transfected with dendriplexes, Cytofectin GSV and control (non-transfected). At 48 h, hVEGF titres had returned to that of the untransfected control for Cytofectin GSV however, a number of dendriplexes continued to exhibit a marked reduction in hVEGF titres.
