144315-64-0Relevant articles and documents
Active immunisation of mice with GnRH lipopeptide vaccine candidates: Importance of T helper or multi-dimer GnRH epitope
Goodwin, Daryn,Simerska, Pavla,Chang, Cheng-Hung,Mansfeld, Friederike M.,Varamini, Pegah,D'Occhio, Michael J.,Toth, Istvan
, p. 4848 - 4854 (2014)
Active immunisation against gonadotropin releasing hormone (GnRH) is a potential alternative to surgical castration. This study focused on the development of a GnRH subunit lipopeptide vaccine. A library of vaccine candidates that contained one or more (up to eight) copies of monomeric or dimeric GnRH peptide antigen, an adjuvanting lipidic moiety based on lipoamino acids, and an additional T helper epitope, was synthesised by solid phase peptide synthesis. The candidates were evaluated in vivo in order to determine the minimal components of this vaccine necessary to induce a systemic immune response. BALB/c mice were immunised with GnRH lipopeptide conjugates, co-administered with or without Complete Freund's Adjuvant, followed by two additional immunisations. Significant GnRH-specific IgG titres were detected in sera obtained from mice immunised with four of the seven lipopeptides tested, with an increase in titres observed after successive immunisations. This study highlights the importance of for epitope optimisation and delivery system design when producing anti-hapten antibodies in vivo. The results of this study also contribute to the development of future clinical and veterinary immunocontraceptives.
2-Aminohydroxamic acid derivatives as inhibitors of Bacillus cereus phosphatidylcholine preferred phospholipase C PC-PLCBc
González-Bulnes, Patricia,González-Roura, Albert,Canals, Daniel,Delgado, Antonio,Casas, Josefina,Llebaria, Amadeu
supporting information; experimental part, p. 8549 - 8555 (2011/02/25)
Phosphatidylcholine preferring phospholipase C (PC-PLC) is an important enzyme that plays a key role in a variety of cellular events and lipid homoeostases. Bacillus cereus phospholipase C (PC-PLCBc) has antigenic similarity with the elusive mammalian PC-PLC, which has not thus far been isolated and purified. Therefore the discovery of inhibitors of PC-PLC Bc is of current interest. Here, we describe the synthesis and biological evaluation of a new type of compounds inhibiting PC-PLCBc. These compounds have been designed by evolution of previously described 2-aminohydroxamic acid PC-PLCBc inhibitors that block the enzyme by coordination of the zinc active site atoms present in PC-PLCBc [Gonzalez-Roura, A.; Navarro, I.; Delgado, A.; Llebaria, A.; Casas, J. Angew. Chem. Int. Ed. 2004, 43, 862]. The new compounds maintain the zinc coordinating groups and possess an extra trimethylammonium function, linked to the hydroxyamide nitrogen by an alkyl chain, which is expected to mimic the trimethylammonium group of the phosphatidylcholine PC-PLCBc substrates. Some of the compounds described inhibit the enzyme with IC 50's in the low micromolar range. Unexpectedly, the most potent inhibitors found are those that possess a trimethylammonium group but have chemically blocked the zinc coordinating functionalities. The results obtained suggest that PC-PLCBc inhibition is not due to the interaction of compounds with the phospholipase catalytic zinc atoms, but rather results from the inhibitor cationic group recognition by the PC-PLCBc amino acids involved in choline lipid binding.
Lipidic Peptides, I Synthesis, Resolution and Structural Elucidation of Lipidic Amino Acids and Their Homo- and Hetero-Oligomers
Gibbons, William A.,Hughes, Richard A.,Charalambous, Mario,Christodoulou, Marika,Szeto, Alice,et al.
, p. 1175 - 1183 (2007/10/02)
The α-amino acids with long alkyl side chains, the so-called lipidic amino acids 1a-e, and their homo-oligomers, the lipidic peptides 1p-aj, represent a class of compounds which combine the structural properties of peptides and proteins with the characteristics of lipids and membranes.The amino acids were synthesised from the appropriate alkyl bromide and diethyl acetamidomalonate.Resolution was made chemically, by forming diastereomers of the amino acid esters with an optically pure α-pinene derivative.The protected homo-oligomers were synthesised in solution with the assistance of a water-soluble carbodiimide coupling agent.In order to modify the physical and chemical properties of the peptides, a series of protected hetero-oligomers were prepared, by similar methods, incorporating either other amino acids (3a-d, 7a-i) or side-chain-substituted lipidic amino acids (6a-d).
