936917-36-1Relevant articles and documents
Discovery of 3,3′-pyrrolidinyl-spirooxindoles as cardioprotectant prohibitin ligands
Elderwish, Sabria,Audebrand, Ana?s,Nebigil, Canan G.,Désaubry, Laurent
supporting information, (2019/11/26)
The scaffold proteins prohibitins-1 and 2 (PHB1/2) play many important roles in coordinating many cell signaling pathways and represent emerging targets in cardiology and oncology. We previously reported that a family of natural products derivatives, flavaglines, binds to PHB1/2 to exert cardioprotectant and anti-cancer effects. However, flavaglines also target the initiation factor of translation eIF4A, which doesn't contribute to cardioprotection and may even induce some adverse effects. Herein, we report the development of a convenient and robust synthesis of the new PHB2 ligand 2′-phenylpyrrolidinyl-spirooxindole, and its analogues. We discovered that these compounds displays cardioprotective effect against doxorubicin mediated cardiotoxicity and uncovered the structural requirement for this activity. We identified in particular some analogues that are more cardioprotectant than flavaglines. Pull-down experiments demonstrated that these compounds bind not only to PHB2 but also PHB1. These novel PHB ligands may provide the basis for the development of new drugs candidates to protect the heart against the adverse effects of anticancer treatments.
Efficient synthesis of diverse heterobifunctionalized clickable oligo(ethylene glycol) linkers: Potential applications in bioconjugation and targeted drug delivery
Goswami, Lalit N.,Houston, Zachary H.,Sarma, Saurav J.,Jalisatgi, Satish S.,Hawthorne, M. Frederick
, p. 1116 - 1126 (2013/03/28)
Herein we describe the sequential synthesis of a variety of azide-alkyne click chemistry-compatible heterobifunctional oligo(ethylene glycol) (OEG) linkers for bioconjugation chemistry applications. Synthesis of these bioorthogonal linkers was accomplished through desymmetrization of OEGs by conversion of one of the hydroxyl groups to either an alkyne or azido functionality. The remaining distal hydroxyl group on the OEGs was activated by either a 4-nitrophenyl carbonate or a mesylate (-OMs) group. The -OMs functional group served as a useful precursor to form a variety of heterobifunctionalized OEG linkers containing different highly reactive end groups, e.g., iodo, -NH2, -SH and maleimido, that were orthogonal to the alkyne or azido functional group. Also, the alkyne- and azide-terminated OEGs are useful for generating larger discrete poly(ethylene glycol) (PEG) linkers (e.g., PEG 16 and PEG24) by employing a Cu(i)-catalyzed 1,3-dipolar cycloaddition click reaction. The utility of these clickable heterobifunctional OEGs in bioconjugation chemistry was demonstrated by attachment of the integrin (αvβ3) receptor targeting peptide, cyclo-(Arg-Gly-Asp-d-Phe-Lys) (cRGfKD) and to the fluorescent probe sulfo-rhodamine B. The synthetic methodology presented herein is suitable for the large scale production of several novel heterobifunctionalized OEGs from readily available and inexpensive starting materials.
Tyrosine bioconjugation through aqueous ene-type reactions: A click-like reaction for tyrosine
Ban, Hitoshi,Gavrilyuk, Julia,Barbas III, Carlos F.
supporting information; experimental part, p. 1523 - 1525 (2010/04/03)
(Figure Presented) A new and versatile class of cyclic diazodicarboxamides that reacts efficiently and selectively with phenols and the phenolic side chain of tyrosine through an ene-like reaction is reported. This mild aqueous tyrosine ligation reaction works over a broad pH range and expands the repertoire of aqueous chemistries available for small molecule, peptide, and protein modification. The tyrosine ligation reactions are shown to be compatible with the labeling of native enzymes and antibodies in a buffered aqueous solution. This reaction provides a novel synthetic approach to bispecific antibodies. We believe this reaction will find broad utility in peptide and protein chemistry and in the chemistry of phenol-containing compounds.
Synthesis and biological evaluation of a series of novel inhibitor of Nek2/Hec1 analogues
Qui, Xiao-Long,Li, Guideng,Wu, Guikai,Zhu, Jiewen,Zhou, Longen,Chen, Phang-Lang,Chamberlin, A. Richard,Lee, Wen-Hwa
supporting information; experimental part, p. 1757 - 1767 (2010/02/28)
High expression in cancer 1 (Hec1) is an oncogene overly expressed in many human cancers. Small molecule inhibitor of Nek2/Hec1 (INH) targeting the Hec1 and its regulator, Nek2, in the mitotic pathway, was identified to inactivate Hec1/Nek2 function media
