Biomedical subjects

Yousef Ahmadibeni

Publications and source records attributed to Yousef Ahmadibeni.

7 recordsLinked to original sources

PubMed2006

Synthesis of polymer-bound 4-acetoxy-3-phenylbenzaldehyde derivatives: applications in solid-phase organic synthesis.

Aminomethyl polystyrene resin was reacted with 4-(5'-formyl-2'-hydroxyphenyl)benzoic acid and 4-(5'-formyl-2'-hydroxyphenyl)phenyl propionic acid, respectively, in the presence of 1-hydroxybenzotriazole and 1,3-diisopropylcarbodiimide to yield polymer-bound benzaldehydes. The phenolic group in resins was acetylated with acetic anhydride to afford two polymer-bound 4-acetoxybenzaldehydes. The reductive amination of polymer-bound linkers by amines and sodium triacetoxyborohydride, followed by sulfonylation with arylsulfonyl chloride derivatives in the presence of pyridine and the cleavage with TFA/DCM/H2O, produced pure sulfonamides.

Benzaldehydes↗

PubMed2006

Solid-phase synthesis of dinucleoside and nucleoside-carbohydrate phosphodiesters and thiophosphodiesters.

Unprotected nucleosides (ROH) were reacted with two polymers bound to N,N-diisopropylamino-1,3,2-oxathiaphospholane in the presence of 1H-terazole. Oxidation with tert-butyl hydroperoxide or sulfurization with Beaucage's reagent, followed by the 1,3,2-oxathiaphospholane ring opening with unprotected nucleosides or carbohydrates (R'OH) in the presence of DBU, afforded nucleoside-(5'-5')-nucleoside or nucleoside-carbohydrate phosphodiester and thiophosphodiester derivatives through the elimination of polymer-bound ethylene episulfide. This strategy offers the advantages of facile isolation of final products and monosubstitution of unprotected nucleosides and carbohydrates.

Carbohydrates↗

PubMed2006

Application of a solid-phase beta-triphosphitylating reagent in the synthesis of nucleoside beta-triphosphates.

A beta-triphosphitylating reagent was subjected to reaction with aminomethyl polystyrene resin-bound p-acetoxybenzyl alcohol to yield the corresponding polymer-bound beta-triphosphitylating reagent. The solid-phase reagent was reacted with unprotected nucleosides (e.g., 3'-azido-3'-deoxythymidine, cytidine, thymidine, uridine, inosine, or adenosine) in the presence of 1H-tetrazole. Polymer-bound nucleosides underwent oxidation with t-butyl hydroperoxide, deprotection of cyanoethoxy groups with DBU, and the acidic cleavage, respectively, to afford only monosubstituted 5'-O-beta-triphosphorylated nucleosides.

Amides↗

PubMed2006

Structural basis for domain-domain communication in a protein tyrosine kinase, the C-terminal Src kinase.

The catalytic activity of protein tyrosine kinases is commonly regulated by domain-domain interactions. The C-terminal Src kinase (Csk) contains a catalytic domain and the regulatory SH3 and SH2 domains. Both the presence of the regulatory domains and binding of specific phosphotyrosine-containing proteins to the SH2 domain activate Csk. The structural basis for both modes of activation is investigated here. First, the SH3-SH2 linker is crucial for Csk activation. Mutagenic and kinetic studies demonstrate that this activation is mediated by a cation-pi interaction between Arg68 and Trp188. Second, Ala scanning and kinetic analyses on residues in the SH2-catalytic domain interface identify three functionally distinct types of residues in mediating the communication between the SH2 and the catalytic domains. Type I residues are important in mediating a ligand-triggered activation of Csk because their mutation severely reduces Csk activation by the SH2 domain ligand. Type II residues are involved in suppressing Csk activity, and their mutation activates Csk, but makes Csk less sensitive to activation by the SH2 ligand. Both type I and type II residues are likely involved in mediating SH2 ligand-triggered activation of Csk. Type III residues are those located in the SH2 domain whose mutation severely decreases Csk catalytic activity without affecting the SH2 ligand-triggered activation. These residues likely mediate SH2 activation of Csk regardless of SH2-ligand interaction. These studies lead us to propose a domain-domain communication model that provides functional insights into the topology of Csk family of protein tyrosine kinases.

Arginine↗

PubMed2005

Selective diphosphorylation, dithiodiphosphorylation, triphosphorylation, and trithiotriphosphorylation of unprotected carbohydrates and nucleosides.

[chemical reaction: see text]. Aminomethyl polystyrene resin-bound linkers of p-acetoxybenzyl alcohol were subjected to reactions with diphosphitylating and triphosphitylating reagents to yield the corresponding polymer-bound diphosphitylating and triphosphitylating reagents, respectively. A number of unprotected carbohydrates and nucleosides were reacted with the polymer-bound reagents. Oxidation with tert-butyl hydroperoxide or sulfurization with Beaucage's reagent, followed by removal of cyanoethoxy group with DBU and the acidic cleavage, respectively, afforded only one type of monosubstituted nucleoside and carbohydrate diphosphates, dithiodiphosphates, triphosphates, and trithiotriphosphates with high regioselectivity.

Alcohols↗

PubMed2005

Polymer-bound oxathiaphospholane: a solid-phase reagent for regioselective monothiophosphorylation and monophosphorylation of unprotected nucleosides and carbohydrates.

Two polymers bound to N,N-diisopropylamino-1,3,2-oxathiaphospholane were reacted with unprotected carbohydrates and nucleosides in the presence of 1H-tetrazole, followed by oxidation with tert-butyl hydroperoxide or sulfurization with Beaucage's reagent. The 1,3,2-oxathiaphospholane ring-opening with 3-hydroxypropionitrile, followed by treatment with DBU, afforded the corresponding monophosphate and monothiophosphate derivatives, respectively, through the elimination of polymer-bound ethylene episulfide. Reactions using this strategy offer the advantages of high regioselectivity, monosubstitution, and facile isolation and recovery of products.

Carbohydrates↗

PubMed2005

Solid-phase reagents for selective monophosphorylation of carbohydrates and nucleosides.

Two classes of aminomethyl polystyrene resin-bound linkers of p-acetoxybenzyl alcohol were subjected to reactions with 2-cyanoethyl N,N-diisopropylchlorophosphoramidite to produce the corresponding polymer-bound phosphitylating reagents. These were reacted with a number of unprotected nucleosides and carbohydrates in the presence of 1H-tetrazole. Oxidation with tert-butyl hydroperoxide followed by removal of the cyanoethoxy group with 1,8-diazabicyclo[5.4.0]undec-7-ene afforded the corresponding polymer-bound phosphate diesters. Acidic cleavage of the p-acetoxybenzyl alcohol linker yielded monophosphorylated products with high regioselectivity and trapped linkers on the resins that can be reused.

Carbohydrate Metabolism↗