1-Aminocyclobutanecarboxylic acid derivatives as novel structural elements in bioactive peptides: application to tuftsin analogs

Journal of Medicinal Chemistry
E GershonovM Fridkin

Abstract

Four novel 2,4-methano amino acids (MAAs, 1-aminocyclobutane-1-carboxylic acids) were synthesized. These include the basic MAA analogs of lysine (16), ornithine (5), and arginine (6) and the neutral methanovaline (22), related to proline. The above MAAs, as well as the MAA analog of homothreonine (7), were incorporated into the peptide chain of the immunomodulatory peptide tuftsin, Thr-Lys-Pro-Arg, known to enhance several biological activities mediated by phagocytic cells. The synthetic methano tuftsin analogs were assayed for their ability to stimulate interleukin-6 (IL-6) secretion by mouse peritoneal macrophages and for their stability in human serum toward enzymatic degradation. It was found that, at 2 x 10(-7) M, [MThr1]tuftsin (24) and an isomer of [MVal3]tuftsin (27a) were considerably more active than the parent peptide in augmentation of cytokine release. [MOrn2]Tuftsin (25) was equally potent. The analogs [MThr1]tuftsin (24) and [MOrn2]tuftsin (25), both pertaining to the proteolytically sensitive Thr-Lys bond of tuftsin, exhibited high resistance to enzymatic hydrolysis as compared to tuftsin. Using specific rabbit anti-tuftsin antibodies in a competitive enzyme-linked immunosorbent assay (ELISA) revealed that none ...Continue Reading

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Citations

Jan 3, 2001·Chirality·S Allenmark, B Lamm
Apr 12, 2008·Journal of Natural Medicines·Valery M Dembitsky
Mar 4, 2000·Advanced Drug Delivery Reviews·A K Agrawal, C M Gupta
Aug 28, 1999·Peptides·I Z Siemion, A Kluczyk
Dec 29, 2004·Journal of Drug Targeting·M Alam KhanO Mohammad
Aug 28, 2010·Contrast Media & Molecular Imaging·Jianghua FengRisto Kauppinen
Sep 23, 2011·Biomaterials·Yingying XuYuanfang Liu
Sep 15, 2016·The Journal of Organic Chemistry·Feng GaoHong Liu
Jul 16, 2010·Journal of Peptide Science : an Official Publication of the European Peptide Society·Nigam Kumar, Raghuvansh Kishore
Apr 10, 2009·The Journal of Organic Chemistry·Andreas A GrauerBurkhard König
Oct 12, 2017·The Journal of Organic Chemistry·Illia O FeskovGünter Haufe
Aug 13, 2005·The Journal of Organic Chemistry·Beatriz M IllescasRosa M Ortuño

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