77611-37-1Relevant articles and documents
Cyclopeptides containing the DEKS motif as conformationally restricted collagen telopeptide analogues: Synthesis and conformational analysis
Wodtke, Robert,Ruiz-Gmez, Gloria,Kuchar, Manuela,Pisabarro, M. Teresa,Novotn, Pavlina,Urbanov, Marie,Steinbach, J?rg,Pietzsch, Jens,L?ser, Reik
, p. 1878 - 1896 (2015)
The collagen telopeptides play an important role for lysyl oxidase-mediated crosslinking, a process which is deregulated during tumour progression. The DEKS motif which is located within the N-terminal telopeptide of the α1 chain of type I collagen has been suggested to adopt a βI-turn conformation upon docking to its triple-helical receptor domain, which seems to be critical for lysyl oxidase-catalysed deamination and subsequent crosslinking by Schiff-base formation. Herein, the design and synthesis of cyclic peptides which constrain the DEKS sequence in a β-turn conformation will be described. Lysine-side chain attachment to 2-chlorotrityl chloride-modified polystyrene resin followed by microwave-assisted solid-phase peptide synthesis and on-resin cyclisation allowed for an efficient access to head-to-tail cyclised DEKS-derived cyclic penta- and hexapeptides. An Nε-(4-fluorobenzoyl)lysine residue was included in the cyclopeptides to allow their potential radiolabelling with fluorine-18 for PET imaging of lysyl oxidase. Conformational analysis by 1H NMR and chiroptical (electronic and vibrational CD) spectroscopy together with MD simulations demonstrated that the concomitant incorporation of a d-proline and an additional lysine for potential radiolabel attachment accounts for a reliable induction of the desired βI-turn structure in the DEKS motif in both DMSO and water as solvents. The stabilised conformation of the cyclohexapeptide is further reflected by its resistance to trypsin-mediated degradation. In addition, the deaminated analogue containing allysine in place of lysine has been synthesised via the corresponding ε-hydroxynorleucine containing cyclohexapeptide. Both ε-hydroxynorleucine and allysine containing cyclic hexapeptides have been subjected to conformational analysis in the same manner as the lysine-based parent structure. Thus, both a conformationally restricted lysyl oxidase substrate and product have been synthetically accessed, which will enable their potential use for molecular imaging of these important enzymes.
CALPAIN MODULATORS AND METHODS OF PRODUCTION AND USE THEREOF
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Paragraph 00445; 00471, (2017/09/27)
The present technology relates to compounds, kits, compositions, and methods useful for the treatment of fibrotic disease. In some aspects, the present technology provides for treatment of various diseases or disorders associated or mediated, at least in part, by calpains, such as CAPN1, CAPN2, and/or CAPN9. The present technology is generally applicable to compounds which inhibit myofibroblast differentiation.
A simple synthesis of 6-hydroxynorleucine based on the rearrangement of an N-nitrosodichloroacetamide
McCarthy, Blaine G.,Macarthur, Nicholas S.,Jakobsche, Charles E.
supporting information, p. 502 - 504 (2016/01/12)
6-Hydroxynorleucine is a versatile chemical intermediate that has found broad use in target-oriented syntheses of numerous biologically active molecules. Despite its widespread use, and despite the various strategies that have been reported for its prepar
Selective inhibitors of plasmepsin II of Plasmodium falciparum on the basis of pepstatin
Rumsh,Mikhailova,Mikhura,Prudchenko,Chikin,Mikhaleva,Kaliberda,Dergousova,Mel'Nikov,Formanovskii
experimental part, p. 660 - 667 (2009/04/07)
A number of new inhibitors of plasmepsin II (PlmII) Plasmodium falciparum, which was one of the key factors of survival of malarial parasite, was synthesized. The inhibitors were analogues of pepstatin with different substitutions for the alanine residue.
Process for producing hydroxyamino acid derivative
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Page 3, (2008/06/13)
Provided is a method of preparing a hydroxyamino acid derivative, particularly in an optically active form thereof with high efficiency. Specifically, provided is a method of preparing hydroxyamino acid derivatives represented by Formula (I) or salts ther
Chemical synthesis of exochelins
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Page column 8, (2008/06/13)
A process for the synthetic generation of high affinity, iron binding compounds known as Exochelins, and more particularly, to a synthetic process for making Exochelins and to modifications to these newly synthesized compounds to vary their physiological properties, including applications of these newly synthesized and utile compounds for diagnosing and treating disease in mammals.
β-strand mimicking macrocyclic amino acids: Templates for protease inhibitors with antiviral activity
Glenn, Matthew P.,Pattenden, Leonard K.,Reid, Robert C.,Tyssen, David P.,Tyndall, Joel D. A.,Birch, Christopher J.,Fairlie, David P.
, p. 371 - 381 (2007/10/03)
New amino acids are reported in which component macrocycles are constrained to mimic tripeptides locked in a β-strand conformation. The novel amino acids involve macrocycles functionalized with both an N- and a C-terminus enabling addition of appendages a
Process for the synthesis of exochelins
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, (2008/06/13)
A process for the synthesis of an Exochelin comprising the steps of generating L-N-[(2-benzyloxy-(benzoyl)] serine or L-N-[2-benzyloxy (benzoyl)] threonine, creating L-N-t-Boc- epsilon -hydroxynorleucine and reacting same to produce L-N-Boc- epsilon -brom
Chemical synthesis of exochelins
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, (2008/06/13)
A process for the synthetic generation of high affinity, iron binding compounds known as Exochelins, and more particularly, to a synthetic process for making Exochelins and to modifications to these newly synthesized compounds to vary their physiological properties, including applications of these newly synthesized and utile compounds for diagnosing and treating disease in mammals.
Collagen cross-links: Synthesis of pyridinoline, deoxypyridinoline and their analogues
Adamczyk, Maciej,Johnson, Donald D.,Reddy, Rajarathnam E.
, p. 63 - 88 (2007/10/03)
An efficient chiral synthesis of (S,S)-(-)-3g, a key intermediate for the preparation of collagen cross-links pyridinoline (Pyd, 1) and deoxypyridinoline (Dpd, 2) was achieved from (4S)-5(tert-butoxy)-4-[(tert- butoxycarbonyl)amino]-5-oxopentanoic acid (21b). Quaternization of (S,S)-(- )-3g with iodide (2S, 5R)-(+)-4a followed by hydrolysiS provided a first chiral synthesis of natural (+)-Pyd (1). 1-(2S)-(+)-Pyd (1) was also synthesized from (S,S)-(-)-3g and iodide (2S, 5S)-(+)-4a. Similarly, quaternization of (S,S)-(-)-3g with iodide (2S)-(-)-4b, which was prepared from (2S)-(-)-6-amino-2[(tert-butoxycarbonyl)amino]hexanoic acid (31) in three steps, followed by hydrolysis afforded natural (+)-Dpd (2) in 5.3% overall yield. Also, the synthesis of racemic Dpd [(±)-2] and a variety of its analogues is presented.
