- Phosphinic peptide matrix metalloproteinase-9 inhibitors by solid-phase synthesis using a building block approach
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The solid-phase synthesis of an array of different pseudopeptides containing a phosphinic glycine-leucine moiety (-GΨ{P(O)OH-CH2}L-)[1] is described. The resulting pseudopeptides were shown to act as matrix metalloproteinase-9 (MMP-9
- Buchardt, Jens,Ferreras, Mercedes,Krog-Jensen, Christian,Delaisse, Jean-Marie,Foged, Niels Taekker,Meldal, Morten
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- Functional examination of novel kisspeptin phosphinic peptides
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Kisspeptins acting on their cognate G protein-coupled receptor, kisspeptin receptor, play important roles in the suppression of cancer cell metastasis and regulation of the reproductive system, and therefore are important for therapeutic intervention. All native functional human kisspeptins (kisspeptin-54, kisspsptin-14 and kisspeptin-13) share the 10 amino acids of kisspeptin-10 at their C-terminus (45-54). However, they are inactivated rapidly by matrix metalloproteinases (MMPs) through the cleavage of the peptide bond between glycine 51 and leucine52, which limits their clinical applications. Development of MMP-resistant analogues of kisspeptins may provide better therapeutic outputs. In the present study, two kisspeptin phosphinic peptides were designed and synthesized, and their ability to induce phosphorylation of ERK1/2 through kisspeptin receptor and their inhibition on MMP-2 and MMP-9 whose activity correlates with cancer metastasis were assessed. The results showed that one analogue, phosphinic kisspeptin R isomer (PKPR), exhibited kisspeptin receptor-agonistic activity and also inhibitory activity on MMP-2, indicating that PKPR may serve as a lead for the further development of kisspeptin analogues for therapeutic purpose.
- Zhang, Xiaoyang,Matziari, Magdalini,Xie, Yixin,Fernig, David,Rong, Rong,Meng, Jia,Lu, Zhi-Liang
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- Synthesis of phosphorus isosters of β-amyloid peptides fragments
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We have developed a synthetic route to pseudo dipeptides, analogs of certain fragments of β-amyloid peptides (products of the APP protein hydrolysis). These compounds can be used for preparation of phosphinic acidic oligopeptides representing the peptide sequence of the β-amyloid but containing the phosphorus isoster peptide fragment. Synthesis of pseudo ornityl-glutamate, pseudo arginyl-glutamate, pseudo glycyl-leucine, and pseudo isoleucyl-glycine via amino- and amidoalkylation of phosphonic acids containing the structural isoster of the corresponding amino acid is described.
- Dmitriev,Ragulin
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p. 2091 - 2098
(2015/11/02)
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