33642-48-7Relevant academic research and scientific papers
Designed semisynthetic protein inhibitors of Ub/Ubl E1 activating enzymes
Lu, Xuequan,Olsen, Shaun K.,Capili, Allan D.,Cisar, Justin S.,Lima, Christopher D.,Tan, Derek S.
supporting information; experimental part, p. 1748 - 1749 (2010/04/25)
(Chemical Equation Presented) Semisynthetic, mechanism-based protein inhibitors of ubiquitin (Ub) and ubiquitin-like modifier (Ubl) activating enzymes (E1s) have been developed to target E1-catalyzed adenylation and thioesterification of the Ub/Ubl C-terminus during the processes of protein SUMOylation and ubiquitination. The inhibitors were generated by intein-mediated expressed protein ligation using a truncated Ub/Ubl protein (SUMO residues 1-94; Ub residues 1-71) with a C-terminal thioester and synthetic tripeptides having a C-terminal adenosine analogue and an N-terminal cysteine residue. SUMO-AMSN (4a) and Ub-AMSN (4b) contain a sulfamide group as a nonhydrolyzable mimic of the phosphate group in the cognate Ub/Ubl-AMP adenylate intermediate in the first half-reaction, and these constructs selectively inhibit SUMO E1 and Ub E1, respectively, in a dose-dependent manner. SUMO-AVSN (5a) and Ub-AVSN (5b) contain an electrophilic vinyl sulfonamide designed to trap the incoming E1 cysteine nucleophile (Uba2 Cys173 in SUMO E1; Uba1 Cys593 in Ub E1) in the second half-reaction, and these constructs selectively, covalently, and stably cross-link to SUMO E1 and Ub E1, respectively, in a cysteine nucleophile-dependent manner. These inhibitors are powerful tools to probe outstanding mechanistic questions in E1 function and can also be used to study the biological functions of E1 enzymes. Copyright
Carbohydrate-based VEGF inhibitors
Haag, Tobias,Hughes, Richard A.,Ritter, Gerd,Schmidt, Richard R.
, p. 6016 - 6033 (2008/09/17)
Cyclic peptide-carbohydrates (compounds 1a-c, 2, 33, 34) were designed and synthesized to act as mimetics of loop 2 of the proangiogenic molecule vascular endothelial growth factor D (VEGF-D). The mimetics were designed to inhibit dimerization of the receptors (VEGFR-2 and VEGFR-3) by VEGF-D, and thus have the potential to inhibit angiogenesis. To this end, in the previously described cyclic octapeptide CNEESLIC and the cyclic nonapeptide CGNEESLIC inhibitors derived from VEGF-D loop 2, the NEES tetrapeptide residue was replaced by a carbohydrate scaffold having the amino acid side chain mimics in positions proposed by modeling studies. Attachment of the additional amino acids using the Fmoc technology, then formation of the cyclic disulfides, and finally total deprotection afforded the target molecules of which 2 and 34 showed an ability to inhibit the biological activity of VEGF-D through VEGFR-2 in cell-based assays, albeit at high mimetic concentration. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.
SYNTHESIS OF A DECAPEPTIDE WITH THE SEQUENCE 1-10 OF HUMAN CALCITONIN WITH MINIMUM PROTECTION OF THE AMINO ACIDS
Zel'tser, I. E.,Tikhomirova, S. P.,Krysin, E. P.,Smirnov, M. B.
, p. 356 - 361 (2007/10/02)
A decapeptide with sequence 1-10 of human calcitonin has been synthesized by a 5 + 5 scheme with the minimum protection of the side-chain functional groups of the amino acid.
